Gene "TOX"
Found 25 records
Gene information
Gene symbol:
TOX
See related:
Ensembl: ENSG00000198846, Gene ID: 9760
Additive variants :
Detected
Genetic interaction partners
No data
Modifier statisitcs
Record:
25 
Disorder:
1 
Vriant:
23 
Reference:
2 
Effect type:
Expressivity(25)  
Modifier effect:
Altered HbF levels(18) ,Altered response to hydroxyurea(7)  
Details：
  • Variant 1:
    TOX:c.925-4761G>A
    Gene:
    TOX
    Genomic location:
    chr8:59744222
    dbSNP ID:
    rs3779999
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 2:
    TOX:c.925-1429A>C
    Gene:
    TOX
    Genomic location:
    chr8:59740890
    dbSNP ID:
    rs826730
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 3:
    TOX:c.693+2349A>G
    Gene:
    TOX
    Genomic location:
    chr8:59761734
    dbSNP ID:
    rs1349115
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 4:
    TOX:c.412-26539A>G
    Gene:
    TOX
    Genomic location:
    chr8:59790903
    dbSNP ID:
    rs765587
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Dominant model: P=0.045 
    Effect:
    Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU
    Reference:
    PMID17299377
    Title:
    Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.
    Species studied:
    Human
    Abstract:
    The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.
  • Variant 5:
    TOX:c.412-25846C>G
    Gene:
    TOX
    Genomic location:
    chr8:59790210
    dbSNP ID:
    rs2594953
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 6:
    TOX:c.411+9191T>G
    Gene:
    TOX
    Genomic location:
    chr8:59842670
    dbSNP ID:
    rs10504269
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 7:
    TOX:c.411+5750A>C
    Gene:
    TOX
    Genomic location:
    chr8:59846111
    dbSNP ID:
    rs6997859
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 8:
    TOX:c.411+3031C>T
    Gene:
    TOX
    Genomic location:
    chr8:59848830
    dbSNP ID:
    rs12155519
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 9:
    TOX:c.411+3031C>T
    Gene:
    TOX
    Genomic location:
    chr8:59848830
    dbSNP ID:
    rs12155519
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Dominant model: P=0.049 
    Effect:
    Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU
    Reference:
    PMID17299377
    Title:
    Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.
    Species studied:
    Human
    Abstract:
    The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.
  • Variant 10:
    TOX:c.168+325T>C
    Gene:
    TOX
    Genomic location:
    chr8:59872177
    dbSNP ID:
    rs1947178
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 11:
    TOX:c.1392+2849T>C
    Gene:
    TOX
    Genomic location:
    chr8:59725048
    dbSNP ID:
    rs2693430
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Dominant model: P=0.044 
    Effect:
    Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU
    Reference:
    PMID17299377
    Title:
    Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.
    Species studied:
    Human
    Abstract:
    The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.
  • Variant 12:
    TOX:c.1392+2396T>G
    Gene:
    TOX
    Genomic location:
    chr8:59725501
    dbSNP ID:
    rs3109904
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 13:
    TOX:c.103-74856G>A
    Gene:
    TOX
    Genomic location:
    chr8:59947423
    dbSNP ID:
    rs9693712
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Dominant model: P=0.037 
    Effect:
    Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU
    Reference:
    PMID17299377
    Title:
    Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.
    Species studied:
    Human
    Abstract:
    The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.
  • Variant 14:
    TOX:c.103-66615T>G
    Gene:
    TOX
    Genomic location:
    chr8:59939182
    dbSNP ID:
    rs851800
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 15:
    TOX:c.103-65076C>T
    Gene:
    TOX
    Genomic location:
    chr8:59937643
    dbSNP ID:
    rs4737532
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 16:
    TOX:c.103-64549A>C
    Gene:
    TOX
    Genomic location:
    chr8:59937116
    dbSNP ID:
    rs389349
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 17:
    TOX:c.103-13745A>T
    Gene:
    TOX
    Genomic location:
    chr8:59886312
    dbSNP ID:
    rs12545204
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 18:
    TOX:c.103-10760T>A
    Gene:
    TOX
    Genomic location:
    chr8:59883327
    dbSNP ID:
    rs10283344
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 19:
    TOX:c.102+73304T>C
    Gene:
    TOX
    Genomic location:
    chr8:59958141
    dbSNP ID:
    rs172652
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Dominant model: P=0.02 
    Effect:
    Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU
    Reference:
    PMID17299377
    Title:
    Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.
    Species studied:
    Human
    Abstract:
    The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.
  • Variant 20:
    TOX:c.102+48913G>C
    Gene:
    TOX
    Genomic location:
    chr8:59982532
    dbSNP ID:
    rs380620
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 21:
    TOX:c.102+48913G>C
    Gene:
    TOX
    Genomic location:
    chr8:59982532
    dbSNP ID:
    rs380620
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Dominant model: P=0.016 
    Effect:
    Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU
    Reference:
    PMID17299377
    Title:
    Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.
    Species studied:
    Human
    Abstract:
    The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.
  • Variant 22:
    TOX:c.1006-3766A>T
    Gene:
    TOX
    Genomic location:
    chr8:59732049
    dbSNP ID:
    rs7821556
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 23:
    TOX:c.1005+468C>T
    Gene:
    TOX
    Genomic location:
    chr8:59738913
    dbSNP ID:
    rs826729
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Dominant model: P=0.016 
    Effect:
    Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU
    Reference:
    PMID17299377
    Title:
    Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.
    Species studied:
    Human
    Abstract:
    The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.
  • Variant 24:
    TOX:c.1005+4542G>C
    Gene:
    TOX
    Genomic location:
    chr8:59734839
    dbSNP ID:
    rs7817609
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
  • Variant 25:
    TOX:c.*1610G>A
    Gene:
    TOX
    Genomic location:
    chr8:59718696
    dbSNP ID:
    rs2726599
    Target disease:
    Sickle Cell Anemia(DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered HbF levels 
    Evidence:
    Bayesian approach 
    Effect:
    Different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
    Reference:
    PMID17918249
    Title:
    Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.
    Species studied:
    Human
    Abstract:
    We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). In subjects aged >or=24 years, 5 SNPs in TOX (8q12.1), 2 SNPs in the beta-globin gene-like cluster, 2 SNPs in the Xp QTL, and 1 SNP in chromosome 15q22 were associated with HbF in the CSSCD and also validated in the MSH. Four other SNPs in 15q22 were associated with HbF only in the larger CSSCD data. When patients aged <24 years in the CSSCD were examined, additional genes, including 4 with roles in nitric oxide metabolism, were associated with HbF level. These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.