Association Of Aminoacyl-tRNA Synthetases Gene Polymorphisms With The Risk Of Congenital Heart Disease In The Chinese Han Population

Congenital heart diseases (CHD) are the most common human birth defects and the leading cause of the perinatal mortality, with an incidence of approximately6-8per live births. The etiology of the CHD is complex and possibly being the interaction of environmental exposures and inherited factors, and nearly13%of CHD attributed to chromosomal variants. While the origin of non-syndromic CHD that accounts for most of all congenital cardiac abnormalities is still under the veil waiting to be further uncovered. Single nucleotide polymorphism (SNP) is an important factor to the susceptibility of human disease, and a plenty of candidate gene polymorphisms were identified to take responsibility for CHD in recent decades.Aminoacyl-tRNA synthetases (ARSs) are in charge of cellular protein synthesis and have additional domains that function versatilely beyond translation. Eight core ARSs (EPRS, MARS, QARS, RARS, IARS, LARS, KARS, DARS) combined with three nonenzymatic components form a complex known as multisynthetase complex (MSC).We hypothesize that the component of MSC gene polymorphisms might influence the susceptibility of sporadic congenital heart disease (CHD). Thus, we conducted a case-control study comprised of984CHD cases and2953non-CHD controls in a Chinese Han population to evaluate the associations of18potentially functional polymorphisms in the member of MSC with the risk of CHD. We observed significant associations with the risk of CHD for rs1061248[odds ratio (OR)=0.90,95%confidence interval (CI)=0.81-0.99], rs2230301[OR=0.73,95%CI=0.60-0.90], rs1061160[OR=1.18,95%CI=1.06-1.31] and rs5030754[OR=1.39,95%CI=1.11-1.75] in EPRS gene. A combined analysis was performed that showed a significant dosage-response effect among individuals carrying the different number of risk alleles and CHD risk (Ptrend=5.00×10-4). Compared with individuals with "0-2" risk allele, those carrying "3","4" or "5or more" risk alleles had a0.97(0.69-1.37),1.25(95%CI=1.05-1.50) or1.38-fold (95%CI=1.14-1.68) increased risk of CHD, respectively. Stratification analysis showed that the genotype distribution between cases and controls of all four SNPs were statistical significant in ASD (P were0.043,0.006,0.006and0.006, respectively),and rs1061160and rs5030754were statistical significant in VSD (P were0.022and0.016), but there was no heterogeneity between different type of CHDs.These findings indicate that genetic variants in EPRS gene may influence the individual susceptibility to CHD in Chinese Han population, and gene polymorphisms of MARS, QARS, RARS, IARS, LARS, KARS and DARS may not be responsible for the occurance of the CHD.