Genetic Polymorphisms in XRCC1, CD3EAP, PPP1R13L, XPB, XPC, and XPF and the Risk of Chronic Benzene Poisoning in a Chinese Occupational Population.
Genetic Polymorphisms in XRCC1, CD3EAP, PPP1R13L, XPB, XPC, and XPF and the Risk of Chronic Benzene Poisoning in a Chinese Occupational Population.
复制标题
XRCC1、CD3EAP、PPP1R13L、XPB、XPC和XPF基因多态性与中国职业人群慢性苯中毒风险。
DOI：
10.1371/journal.pone.0144458
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lu X
中科院分区：
文献类型：
--
作者：
Xue P;Gao L;Xiao S;Zhang G;Xiao M;Zhang Q;Zheng X;Cai Y;Jin C;Yang J;Wu S;Lu X
DNA修复机制缓解苯致DNA损伤的能力的个体差异可能是慢性苯中毒的关键，慢性苯中毒在中国是一种日益普遍的职业病。ERCC1(切除修复交叉互补组1)位于染色体19q13.2-3上，参与核苷酸切除修复(NER)的关键步骤；此外，我们在以前的报告中确定ERCC1 rs11615是CBP易感性的生物标志物。我们的目的是进一步探索与ERCC1基因多态性相关的一些遗传变异与CBP风险之间的更深层次的联系。应用Snapshot和TaqMan-MGB®探针技术，对XRCC1、CD3EAP、PPP1R13L、XPB(B组)、XPC(C组)和XPF(F组)的9个单核苷酸多态(SNPs)进行了基因分型。通过分层分析评估了这些SNPs与吸烟和饮酒等生活方式因素之间的潜在交互作用。即使对潜在的混杂因素进行分层，XRCC1等位基因rs25487仍与较高的慢性BP风险相关(P<；0.001)。饮酒者(OR=8.000；95%CI：1.316~48.645；P=0.022)、男性(OR=9.333；95%CI：1.593~54.672；P=0.019)、≤暴露12年(OR=2.612；95%CI：1.048~6.510；P=0.035)的携带者患慢性BP的危险性增加。然而，PPP1R13Lrs1005165的T等位基因和CD3EAP rs967591的GA等位基因(OR=0.162；95%CI：0039~0.666；P=0.037)降低了男性慢性BP的风险。XRCC1的单倍型分析表明，XRCC1的rs25487A、rs25489G和rs1799782T(OR=15.469；95%CI：5.536~43.225；P<；0.001)与慢性支气管炎的高危相关。结果表明，XRCC1基因rs25487和rs1799782多态性可能与CBP的易感性有关，可作为有效的生物标志物。总体而言，染色体19q13.2-3上的基因在中国职业性暴露人群慢性BP的发生发展中可能具有特殊的意义。
Individual variations in the capacity of DNA repair machinery to relieve benzene-induced DNA damage may be the key to developing chronic benzene poisoning (CBP), an increasingly prevalent occupational disease in China. ERCC1 (Excision repair cross complementation group 1) is located on chromosome 19q13.2–3 and participates in the crucial steps of Nucleotide Excision Repair (NER); moreover, we determined that one of its polymorphisms, ERCC1 rs11615, is a biomarker for CBP susceptibility in our previous report. Our aim is to further explore the deeper association between some genetic variations related to ERCC1 polymorphisms and CBP risk. Nine single nucleotide polymorphisms (SNPs) of XRCC1 (X-ray repair cross-complementing 1), CD3EAP (CD3e molecule, epsilon associated protein), PPP1R13L (protein phosphatase 1, regulatory subunit 13 like), XPB (Xeroderma pigmentosum group B), XPC (Xeroderma pigmentosum group C) and XPF (Xeroderma pigmentosum group F) were genotyped by the Snapshot and TaqMan-MGB® probe techniques, in a study involving 102 CBP patients and 204 controls. The potential interactions between these SNPs and lifestyle factors, such as smoking and drinking, were assessed using a stratified analysis. An XRCC1 allele, rs25487, was related to a higher risk of CBP (P<0.001) even after stratifying for potential confounders. Carriers of the TT genotype of XRCC1 rs1799782 who were alcohol drinkers (OR = 8.000; 95% CI: 1.316–48.645; P = 0.022), male (OR = 9.333; 95% CI: 1.593–54.672; P = 0.019), and had an exposure of ≤12 years (OR = 2.612; 95% CI: 1.048–6.510; P = 0.035) had an increased risk of CBP. However, the T allele in PPP1R13L rs1005165 (P<0.05) and the GA allele in CD3EAP rs967591 (OR = 0.162; 95% CI: 0039~0.666; P = 0.037) decreased the risk of CBP in men. The haplotype analysis of XRCC1 indicated that XRCC1 rs25487A, rs25489G and rs1799782T (OR = 15.469; 95% CI: 5.536–43.225; P<0.001) were associated with a high risk of CBP. The findings showed that the rs25487 and rs1799782 polymorphisms of XRCC1 may contribute to an individual’s susceptibility to CBP and may be used as valid biomarkers. Overall, the genes on chromosome 19q13.2–3 may have a special significance in the development of CBP in occupationally exposed Chinese populations.