Variant "SMAD3:c.206+6924A>G"
Search results: 2 records
Variant information
Gene:
SMAD3 
Variant:
SMAD3:c.206+6924A>G 
Genomic location:
chr15:67365622(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_005902.3:c.206+6924A>G
dbSNP ID:
rs10518707  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(1) ,Pleiotropy(1)  
Modifier effect:
Altered HbF levels(1) ,Bacteremia-prone phenotype(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:
    Pleiotropy 
    Modifier effect:
    Bacteremia-prone phenotype 
    Evidence:
    P=0.0114 
    Effect:
    We suggest that both IGF1R and the TGF-beta /BMP pathway could play important roles in immune function in sickle cell anemia and their polymorphisms may help identify a bacteremia-prone phenotype.
    Reference:
    PMID16886151
    Title:
    Association of polymorphisms of IGF1R and genes in the transforming growth factor- beta /bone morphogenetic protein pathway with bacteremia in sickle cell anemia.
    Species studied:
    Human
    Abstract:
    Infection and bacteremia are common in sickle cell disease. We hypothesized that, consistent with evidence for the genetic modulation of other disease complications, the risk of developing bacteremia might also be genetically modulated. Accordingly, we studied the association of single nucleotide polymorphisms (SNPs) in candidate genes with the risk of bacteremia in sickle cell anemia. We found significant associations with SNPs in IGF1R and genes of the TGF-beta /BMP pathway (BMP6, TGFBR3, BMPR1A, SMAD6 and SMAD3). We suggest that both IGF1R and the TGF-beta /BMP pathway could play important roles in immune function in sickle cell anemia and their polymorphisms may help identify a bacteremia-prone phenotype.