Genetic variants in multisynthetase complex genes are associated with DNA damage levels in Chinese populations
Genetic variants in multisynthetase complex genes are associated with DNA damage levels in Chinese populations
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多合成酶复合体基因的遗传变异与中国人群的 DNA 损伤水平相关
DOI：
10.1016/j.mrfmmm.2016.01.006
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发表时间：
2016-04-01
影响因子：
2.3
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
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作者：
Liu, Jia;Zhu, Meng;Shen, Hongbing
氨酰-tRNA合成酶（ARSs）与ARS-interacting multiple functional proteins（AIMPs）形成多合成酶复合物（MSC），在DNA损伤修复过程中发挥重要作用。我们假设，在关键的ARS和AIMPs的遗传变异可能会调节DNA损伤反应。因此，我们系统地筛选了MSC基因中的23个潜在的功能多态性，并评估了遗传变异与DNA损伤水平之间的关联，307名受试者来自中国南方、中部和北方三个城市（分别为珠海、武汉和天津）。我们检查了每个受试者的个人24小时PM2.5暴露水平和外周血淋巴细胞DNA损伤水平。我们发现AIMP 3中rs 12199241的变异等位基因与DNA损伤水平显著相关（β = 0.343，95%CI：0.133-0.554，P=0.001）。同时，rs 5030754在EARS和rs3784929在KARS中的结果表明它们在DNA损伤过程中的作用（rs 5030754的beta = 0.331，95%CI：0.062-0.599，P=0.016; rs3784929的beta=0.192，95%CI：0.016-0.368，P=0.033）。经过多次测试，rs 12199241仍然与DNA损伤水平显著相关。这三种多态性的联合分析显示，风险等位基因的数量与较高的DNA损伤水平之间存在显著的等位基因剂量相关性（P趋势< 0.001）。这些发现表明，MSC基因的遗传变异可能是中国人群中PM2.5调节的DNA损伤水平的原因。(C)2016由Elsevier B. V.出版
Aminoacyl-tRNA synthetases (ARSs) and ARS-interacting multi-functional proteins (AIMPs) form a multisynthetase complex (MSC) and play an important role in the process of DNA damage repair. We hypothesized that genetic variants in key ARSs and AIMPs might regulate the DNA damage response. Therefore, we systematically screened 23 potentially functional polymorphisms in MSC genes and evaluated the association between the genetic variants and DNA damage levels in 307 subjects from three cities in southern, central and northern China (Zhuhai, Wuhan and Tianjin, respectively). We examined personal 24-h PM2.5 exposure levels and DNA damage levels in peripheral blood lymphocytes for each subject. We found that the variant allele of rs12199241 in AIMP3 was significantly associated with DNA damage levels (beta = 0.343, 95%CI: 0.133-0.554, P=0.001). Meanwhile, the results of rs5030754 in EARS and rs3784929 in KARS indicated their suggestive roles in DNA damage processes (beta = 0.331, 95%CI: 0.062-0.599, P=0.016 for rs5030754; beta=0.192, 95%CI: 0.016-0.368, P=0.033 for rs3784929, respectively). After multiple testing, rs12199241 was still significantly associated with DNA damage levels. Combined analysis of these three polymorphisms showed a significant allele-dosage association between the number of risk alleles and higher DNA damage levels (P-trend < 0.001). These findings indicate that genetic variants in MSC genes may account for PM2.5-modulated DNA damage levels in Chinese populations. (C) 2016 Published by Elsevier B.V.