Association Of PABPC1 And SESN2 Gene Polymorphisms With Congenital Heart Disease Susceptibility In Chinese Population

Background:Congenital heart defect (CHD) is one of the most common birth defects and the leading cause of infant morbidity, which seriously affects human living quality and plays heavy burden to families as well as society. Congenital heart defect has a multifactorial origin, in which multiple subtle genetic factors and peri-conception environmental exposures interact. In recent years, the research of CHD genetic etiology made a significant breakthrough along with popularization of genome sequence and gene array. Extensive scientific research confirms that PABPC1 is essential for early embryonic development in many model organisms. Morpholino-mediated knockdown of PABPC1 causes multiple organ malformations even embryonic lethality. Meanwhile, the results of genome-wide exome sequencing in the family of congenital heart disease indicated that PABPC1 SESN2 might be the candidate genes of the disease. The present study aimed to investigate the relationship between PABPC1 and SESN2 gene polymorphism and CHD susceptibility in Chinese population.Methods:A case-control association study in individuals with CCSDs (Congenital Cardiac Septal Defects, n=574) and healthy controls (n=488) was conducted. The strategy that tagSNPs (MAF≥0.1) cover the whole gene was employed. Three tagSNPs (rs1039153, rs1786321, rs3132872) in PABP1 gene and two tagSNPs (rs580800, rs543240) in SESN2 were genotyped by combined PCR-RFLP with nucleic acid sequencing.Associations were analyzed by chi-square test in SPSS 17.0. It was considered that p value less than 0.05 have statistically significant difference. And haplotypes were reconstructed using the SHEsis.Results:Only genotype frequencies of rs1786321 of PABP1 gene have significant diversity between CHD patients and healthy controls in the recessive genetic model (P=0.032).And it was found that the diversity become more remarkable between the VSD subgroups and controls (P=0.005). The frequencies of rs3132872 T allele had significant difference between VSD groups and controls in the dominant genetic model (P=0.020).Moderate or strong linkage disequilibrium was found among the three tagSNPs in PABP1. Haplotype analysis revealed CGC and TCC were associated with increased risk of CHD, while TGC appeared to be a protective haplotype for CHD.The frequencies of genotype or allele of the two tagSNPs in SESN2 gene were not significantly different between CHD patients and healthy controls.Conclusion:The study is the first report for the association between PABPC1 gene polymorphism and CHD in Chinese population. It was found that rs3132872 and rsl786321 in PABPC1 gene were significantly associated with CCSD, especially with VSD. The PABPC1 gene might be a potential susceptibility gene of congenital heart defect in Chinese Population. There might be no association between CHD and SESN2 in Chinese Population.