title: Association of two variants in SMAD7 with the risk of congenital heart disease in the Han Chinese population.
abstract: SMAD7 is a general antagonist of TGF-β signaling and has been found to be involved in cardiogenesis in mouse models, but its role in human congenital heart disease (CHD) has yet to be investigated. To examine if SMAD7 is associated with CHD, we conducted a case-control study in the Han Chinese population. Exon1 and exon4 of SMAD7, which encode the functional MH1 and MH2 domains, were directly sequenced in 1,201 sporadic CHD patients and 1,116 control individuals. A total of 18 sequence variations were identified. Two common variants rs3809922 and rs3809923 are located at exon4 of SMAD7, and were found in strong linkage disequilibrium with each other (r² = 0.93). We analyzed the association of these two loci with CHD in 3 independent subgroup case-control studies, and found that in some subgroups, rs3809922 and rs3809923 were significantly associated with CHD through genetic model analysis. In the combined data set, TT genotype in rs3809922 significantly increased the risk of CHD compared with CC and CT, while GG genotype in rs3809923 significantly increased the risk of CHD compared with CC and CG, particularly in the recessive model. In addition, haplotype analyses showed that haplotype TG significantly increased the risk of CHD (P = 6.9×10⁻⁶); this finding supports the results from the analyses based on single locus. According to data from the 1000 Genomes Project, the frequencies of the two risk alleles varied greatly between populations worldwide, which indicate the identified associations might have a population difference. To our knowledge, this is the first report that genetic variants in SMAD7 influence susceptibility to CHD risk.
authors.affiliation: Chinese Academy of Sciences and Max Planck Society (CAS-MPG) Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China ; The State Key Laboratory of Genetic Engineering and Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Erli
authors.initials: E
authors.lastname: Wang
authors.forename: Wenfei
authors.initials: W
authors.lastname: Jin
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Duan
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
authors.forename: Shuna
authors.initials: S
authors.lastname: Sun
authors.forename: Guoying
authors.initials: G
authors.lastname: Huang
authors.forename: Kaihu
authors.initials: K
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006330:Heart Defects, Congenital / Q000235:genetics; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D051906:Smad7 Protein / Q000235:genetics*
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein
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