Abstract
BackgroundVentricular 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.MethodsIn 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.ResultsWe 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).ConclusionsThese findings indicate that genetic variants of the DARS gene may influence individual susceptibility to isolated VSD in the Chinese Han population.
Highlights
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 Congenital heart defects (CHDs)
We systematically investigated the association of potentially functional single nucleotide polymorphisms (SNPs) with VSD susceptibility in 841 cases and 2953 controls in a Chinese population
The A allele of rs2164331 was associated with a decreased risk of VSD [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.69-0.91, P = 3.17 × 10-3]; the A allele of rs6738266 and the G allele of rs309143 were associated with an increased risk of VSD (OR = 1.17, 95% CI = 1.05-1.29, P = 2.83 × 10-3, and OR = 1.09, 95% CI = 1.01-1.17, P = 3.12 × 10-2, respectively)
Summary
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. Four single nucleotide polymorphisms (SNPs) in EPRS have been reported to be associated with risks of CHD in Chinese populations. Congenital heart defects (CHD) are the most common major human birth malformation, affecting approximately 8 per 1,000 live births [1, 2]. CHD are associated with significant morbidity and mortality and are second only to infectious diseases with respect to contributing to infant mortality rate [3]. The origin of isolated VSD is waiting to be uncovered further [10]
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