Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.
Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.
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DOI：
10.1186/s12940-017-0283-8
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Ahsan H
中科院分区：
文献类型：
--
作者：
Kibriya MG;Jasmine F;Parvez F;Argos M;Roy S;Paul-Brutus R;Islam T;Ahmed A;Rakibuz-Zaman M;Shinkle J;Slavkovich V;Graziano JH;Ahsan H
饮用水中的砷暴露是一个全球性的健康问题，砷诱发的皮肤损伤是慢性砷中毒的标志。我们和其他人已经报道了生殖系遗传变异是这种皮肤病变的危险因素。拷贝数变异（CNV）在种系DNA中在这方面的作用尚不清楚。从大量的前瞻性随访队列中，我们随机选择了2171名在入组时没有砷诱导皮肤病变的受试者，并在Illumina Cyto12v2.1 SNP芯片上对他们的全血DNA样本进行基因分型，以生成DNA拷贝数。参与者每2年随访一次，共随访8年，特别是对皮肤病变的发展。在Cox回归模型中，每个CNV片段被用作预测因子，考虑其他潜在的协变量，用于皮肤病变的发生率。许多基因（OR5J2、GOLGA6L7P、APBA2、GALNTL5、VN1R31P、PHKG1P2、SGCZ、ZNF658）和lincRNA基因（RP11-76I14.1、CTC-535 M15.2、RP11-73B2.2）存在基因组缺失，与性别、年龄和砷暴露无关，导致皮肤病变发生的风险更高[HR在1.67 （CI 1.3-2.1）和2.15 （CI 1.5-2.9）之间]。一些缺失在特定性别中有更强的影响（男性的ZNF658，女性的SGCZ），一些缺失在高砷暴露中有更强的影响（lincRNA CTD-3179P9.1），这表明可能存在基因-环境相互作用。这项首次对暴露于砷的大队列进行前瞻性随访的全基因组CNV研究表明，几个基因和lincRNA基因的DNA缺失可能使个体易患砷诱导的皮肤病变。本文的在线版本（doi:10.1186/s12940-017-0283-8）包含补充材料，可供授权用户使用。
Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown. From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2.1 SNP chips to generate DNA copy number. Participants were followed up every 2 years for a total of 8 years, especially for the development of skin lesions. In Cox regression models, each CNV segment was used as a predictor, accounting for other potential covariates, for incidence of skin lesions. The presence of genomic deletion(s) in a number of genes (OR5J2, GOLGA6L7P, APBA2, GALNTL5, VN1R31P, PHKG1P2, SGCZ, ZNF658) and lincRNA genes (RP11-76I14.1, CTC-535 M15.2, RP11-73B2.2) were associated with higher risk [HR between 1.67 (CI 1.3-2.1) and 2.15 (CI 1.5-2.9) for different CNVs] for development of skin lesions independent of gender, age, and arsenic exposure. Some deletions had stronger effect in a specific gender (ZNF658 in males, SGCZ in females) and some had stronger effect in higher arsenic exposure (lincRNA CTD-3179P9.1) suggesting a possible gene-environment interaction. This first genome-wide CNV study in a prospectively followed-up large cohort, exposed to arsenic, suggests that DNA deletion in several genes and lincRNA genes may predispose an individual to a higher risk of development of arsenic-induced skin lesions. The online version of this article (doi:10.1186/s12940-017-0283-8) contains supplementary material, which is available to authorized users.
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