中国汉族人群中DARS基因多态性与单纯性室间隔缺损风险的关联。

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

作者信息

Feng Yu, Chen Runsen, Mo Xuming

机构信息

Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, China.

出版信息

Ital J Pediatr. 2016 Nov 21;42(1):102. doi: 10.1186/s13052-016-0311-2.

DOI:10.1186/s13052-016-0311-2

PMID:27871331

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5117545/

Abstract

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], rs6738266 [G/A; OR = 1.17, 95% CI = 1.05-1.29, P = 1.83 × 10], and rs309143 [G/A; OR = 1.09, 95% CI = 1.01-1.17; P = 3.12 × 10]. 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 (P = 6.37 × 10).

CONCLUSIONS

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

摘要

背景

室间隔缺损（VSD）是先天性心脏病（CHD）最常见的亚型，估计占所有CHD病例的20%至30%。孤立性VSD的病因仍知之甚少。八种核心氨酰-tRNA合成酶（ARSs）（EPRS、MARS、QARS、RARS、IARS、LARS、KARS和DARS）与三种非酶成分结合形成一种称为多合成酶复合物（MSC）的复合物。据报道，EPRS中的四个单核苷酸多态性（SNPs）与中国人群患CHD的风险相关。

方法

在本研究中，我们假设DARS基因的SNPs可能影响散发性孤立性VSD的易感性。因此，我们对841例孤立性VSD患者和2953例来自中国汉族人群的非CHD对照进行了病例对照研究，以评估DARS基因内4个潜在功能性SNPs与VSD风险的相关性。

结果

我们观察到，VSD风险与rs2164331 [G/A；优势比（OR）=0.78，95%置信区间（CI）=0.69-0.91；P=3.17×10]、rs6738266 [G/A；OR=1.17，95%CI=1.05-1.29，P=1.83×10]和rs309143 [G/A；OR=1.09，95%CI=1.01-1.17；P=3.12×10]显著相关。此外，与携带0-2个风险等位基因的个体相比，携带3个、4个和5个或更多风险等位基因的个体患VSD的风险分别高1.01倍、1.22倍和1.46倍。这些发现揭示了携带不同数量风险等位基因的个体中VSD风险存在显著的剂量反应效应（P=6.37×10）。