Association of Aminoacyl-tRNA Synthetases Gene Polymorphisms with the Risk of Congenital Heart Disease in the Chinese Han Population

Aminoacyl-tRNA synthetases (ARSs) are in charge of cellular protein synthesis and have additional domains that function in a versatile manner beyond translation. Eight core ARSs (EPRS, MRS, QRS, RRS, IRS, LRS, KRS, DRS) combined with three nonenzymatic components form a complex known as multisynthetase complex (MSC). We hypothesize that the single-nucleotide polymorphisms (SNPs) of the eight core ARS coding genes might influence the susceptibility of sporadic congenital heart disease (CHD). Thus, we conducted a case-control study of 984 CHD cases and 2953 non-CHD controls in the Chinese Han population to evaluate the associations of 16 potentially functional SNPs within the eight ARS coding genes with the risk of CHD. We observed significant associations with the risk of CHD for rs1061248 [G/A; odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.81-0.99; P = 3.81 x 10(-2)], rs2230301 [A/C; OR = 0.73, 95%CI = 0.60-0.90, P = 3.81 x 10(-2)], rs1061160 [G/A; OR = 1.18, 95%CI = 1.06-1.31; P = 3.53 x 10(-3)] and rs5030754 [G/A; OR = 1.39, 95%CI = 1.11-1.75; P = 4.47 x 10(-3)] of EPRS gene. After multiple comparisons, rs1061248 conferred no predisposition to CHD. Additionally, a combined analysis showed a significant dosage-response effect of CHD risk among individuals carrying the different number of risk alleles (P-trend = 5.00 x 10(-4)). Compared with individuals with 0-2 risk allele, those carrying 3, 4 or 5 or more risk alleles had a 0.97-, 1.25- or 1.38-fold increased risk of CHD, respectively. These findings indicate that genetic variants of the EPRS gene may influence the individual susceptibility to CHD in the Chinese Han population.