Variant "FLT1:c.1436+3896C>T"
Search results: 3 records
Variant information
Gene:
FLT1 
Variant:
FLT1:c.1436+3896C>T 
Genomic location:
chr13:28997400(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_002019.4:c.1436+3896C>T
protein_coding NM_001160030.1:c.1436+3896C>T
protein_coding NM_001159920.1:c.1436+3896C>T
protein_coding NM_001160031.1:c.1436+3896C>T
dbSNP ID:
rs8002446  
GWAS trait:
no data 
Modifier statisitcs
Record:
3 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(3)  
Modifier effect:
Altered response to hydroxyurea(2) ,Altered HbF levels(1)  
Details：
  • 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.
  • Target disease:
    Sickle Cell Anemia (DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Recessive model: P=0.01 
    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.
  • Target disease:
    Sickle Cell Anemia (DOID_10923)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered response to hydroxyurea 
    Evidence:
    Recessive model: P=0.011 
    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.