TGFBR2 Association Study Polymorphism And Congenital Heart Disease And Rheumatic Heart Disease

Part I Association study of TGFBR2gene polymorphism and congenital heart diseaseBackground and objective Congenital heart disease (CHD) represents the most congenital malformation, with the incidence of9.1‰among live births. CHD is the most important cause of death in infants than any other condition when infectious etiologies are excluded. The etiology of CHD is still not completely understood. It is considered that genetic factors interact with environmental factors to cause CHD. Transforming growth factor-β (TGF-β) signaling pathway plays a crucial role in cardiac development. Transforming growth factor-β receptor II (TGFBR2) is a key component of TGF-β signaling pathway. TGFBR2can be detected in the generation of heart and the mouse embryos of TGFBR2gene knockout exhibited congenital heart defects. This study aimed to explore the association between TGFBR2gene polymorphisms and congenital heart disease. We expect to supply new theoretic evidence for pathogenesis of CHD.Methods The research design was a case-control study. A total of115patients who were hospitalized in Nanjing First Hospital Affiliated to Nanjing Medical University between October2008and December2010with CHD served as cases while we collected615healthy adults from communities as controls. Two tagging single nucleotide polymorphisms (tagSNPs) in5’upstream of TGFBR2gene (rs6785358and rs764522) were selected and genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay.Results The distribution of genotypes in controls did not deviate significantly from Hardy-Weinberg equilibrium for rs6785358or rs764522(P>0.05). A significant difference was seen in the distribution of genotypes between cases and controls for rs6785358(P=0.041). For rs6785358the carrier of the G allele (AG/GG genotype) showed a significantly higher risk of CHD compared with AA homozygotes (OR=1.543,95%CI:1.015-2.347). Further analysis by sex stratification indicated that individuals carrying G allele (AG/GG genotype) for SNP rs6785358have a higher susceptibility to CHD in males (OR=2.088,95%CI:1.123-3.883), but not females (OR=1.195,95%CI:0.666-2.146). No statistical significance was detected in the distribution of genotypes and allele frequencies for rs764522between cases and controls (P>0.05). We also evaluate the effects of the TGFBR2gene rs6785358and rs764522polymorphisms on certain types of CHD, but we observed no significant difference in the distribution of genotypes and allele frequencies for the two SNPs between cases and controls (P>0.05).Conclusion Our result revealed that rs6785358polymorphism of TGFBR2gene was associated with increased risk of CHD in Han Chinese men. Part II Association study of TGFBR2gene polymorphism and rheumatic heart diseaseBackground and objective Rheumatic heart disease (RHD) is a complex disease with involvement of genetic as well as environmental factors in its pathogenesis. Transforming growth factor-β1(TGF-β1) plays some role in valvular fibrosis and calcification in RHD. To conduct effects, TGF-β1must first bind to transforming growth factor-β receptor type II (TGFBR2) on the cell surface. And The expression level of TGFBR2can influence the pathway activation status of TGF-β signaling pathway and the specific response of cells to TGF-β. However, the role of TGFBR2in RHD has not been studied. This study aimed to explore the association between TGFBR2gene polymorphisms and rheumatic heart disease.Methods The research design was a case-control study. A total of207patients who were hospitalized in Nanjing First Hospital Affiliated to Nanjing Medical University between October2008and January2011with RHD served as cases while we collected615age and gender matched healthy adults from communities as controls. Two tagging single nucleotide polymorphisms (tagSNPs) in5’upstream of TGFBR2gene (rs6785358and rs764522) were selected and genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay.Results The distribution of genotypes in controls did not deviate significantly from Hardy-Weinberg equilibrium for rs6785358or rs764522(P>0.05). The frequencies of genotype AA, AG and GG of rs6785358in cases and controls were72.0%,25.1%,2.9%and68.9%,28.0%,3.1%, respectively. There was no significant difference in the distribution of genotype frequencies for rs6785358between cases and controls (χ2=0.50, P=0.78). The frequencies of allele A and G of rs6785358in cases and controls were84.5%,15.5%and82.9%,17.1%, respectively. There was no significant difference in the distribution of allele frequencies for rs6785358between cases and controls (χ2=0.43, P=0.51). The frequencies of genotype CC, CG and GG of rs764522in cases and controls were77.3%,21.3%,1.4%and75.6%,21.3%,3.1%, respectively. There was no significant difference in the distribution of genotype frequencies for rs764522between cases and controls (χ2=1.33, P=0.51). The frequencies of allele C and G of rs764522in cases and controls were87.9%,12.1%and86.2%,13.8%, respectively. There was no significant difference in the distribution of allele frequencies for rs764522between cases and controls (χ2=0.55, P=0.46). Further analysis by sex stratification showed that no statistical significance was detected in the distribution of genotype and allele frequencies for rs6785358or rs764522between cases and controls.Conclusion TGFBR2gene rs6785368and rs764522polymorphisms are not associated with RHD in Chinese Han people.