Association of DARS gene polymorphisms with the risk of isolated ventricular septal defects in the Chinese Han population.

BACKGROUND: Ventricular septal defects (VSD) are the most common subtype of congenital heart defects (CHD) and are estimated to account for 20 to 30% of all cases of CHD. The etiology of isolated VSD remains poorly understood. Eight core aminoacyl-tRNA synthetases (ARSs) (EPRS, MARS, QARS, RARS, IARS, LARS, KARS, and DARS) combine with three nonenzymatic components to form a complex known as the multisynthetase complex (MSC). Four single nucleotide polymorphisms (SNPs) in EPRS have been reported to be associated with risks of CHD in Chinese populations.

METHODS: In this study, we hypothesize that SNPs of the DARS gene might influence susceptibility to sporadic isolated VSD. Therefore, we conducted a case-control study of 841 patients with isolated VSD and 2953 non-CHD controls from the Chinese Han population to evaluate how 4 potentially functional SNPs within the DARS gene were associated with the risk of VSD.

RESULTS: We observed that the risk of VSD was significantly associated with rs2164331 [G/A; odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.69-0.91; P = 3.17 × 10(-3)], rs6738266 [G/A; OR = 1.17, 95% CI = 1.05-1.29, P = 1.83 × 10(-3)], and rs309143 [G/A; OR = 1.09, 95% CI = 1.01-1.17; P = 3.12 × 10(-2)]. Additionally, compared with individuals with 0-2 risk alleles, individuals carrying 3, 4, and 5 or more risk alleles had 1.01-, 1.22- and 1.46-fold greater risks of VSD, respectively. These findings revealed a significant dose-response effect for VSD risk among individuals carrying different numbers of risk alleles (Ptrend = 6.37 × 10(-4)).

CONCLUSIONS: These findings indicate that genetic variants of the DARS gene may influence individual susceptibility to isolated VSD in the Chinese Han population.