Association Of Notch1and SESN2Gene Variants With Congenital Heart Disease In Northwest Chinese Population

Background:Congenital heart diseases (CHDs) are a common congenital birth defect, the etiologies of which are complex and associated with both genetic and environmental factors, sporadic heart disease accounting for more than90%. Recent studies have demonstrated that Notch signaling pathway may play an important role in the development of endocardial cushion, which is closely related to atrioventricular septal and valve. Because of the inherited factors which involved in the development of multi-gene diseases have clearly regional and ethnic differences, so this study aims to evaluate the association of Notch1and SESN2gene polymorphisms and CHD in northwest Chinese population.Methods:389CHD patients and411normal controls were genotyped for three SNPs of Notchl and SESN2gene in a case-control study, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-denaturing high performance liquid chromatography (PCR-DHPLC), SPSS17.0were used to correlation analysis.Results:The genotype frequencies of rs3124602AA and rs10521GG were significantly different in CHD patients than that in controls, with p-value=0.002, odds ratio (OR)=1.919,95%confidence interval (95%CI):1.266-2.907, and rs10521with p-value=0.034, OR=2.090,95%CI:1.044-4.186, respectively. In addition, the homozygote AA genotype and allele A of rs3124602were associated with increased risk for ventricular septal defect (VSD; p-value=1.370E-4, OR=2.471,95%CI:1.543-3.959; p-value=3.375E-5, OR=1.594,95%CI:1.278-1.989, respectively), whereas the homozygote GG genotype of rs10521was associated with increased risk for atrial septal defect (ASD, p-value=0.005, OR=3.291,95%CI:1.388-7.803). After classification according to anatomical location, the statistical associations of these two SNPs were mainly in Membranous VSD and Secundum ASD. Haplotype analysis showed that haplotype TAA and TGA had significant association with CHD risk, TAA was an risk haplotype (P=0.011,OR=1.450,95%CI=1.087-1.933),TGA was a protective haplotype (P=0.006, OR=0.641,95%CI=0.464-0.885。 Conclusion:This is the first report for the association between Notch1gene polymorphism and CHD in Chinese population. SNP rs3124602is significantly associated with VSD, and SNP rs10521is significantly related to ASD. Notch1may be a candidate gene to CHD in Chinese population.