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肾功能与 EGFR 和 TNF-α 基因多态性对金属工业工人和普通人群血浆金属的影响。

The Association of Renal Function and Plasma Metals Modified by EGFR and TNF-α Gene Polymorphisms in Metal Industrial Workers and General Population.

机构信息

Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan.

出版信息

Int J Environ Res Public Health. 2021 Aug 25;18(17):8965. doi: 10.3390/ijerph18178965.

Abstract

Exposure to metals may be associated with renal function impairment, but the effect modified by genetic polymorphisms was not considered in most studies. Epidermal growth factor receptor (EGFR) and tumor necrotic factor-α (TNF-α) play important roles in renal hemodynamics, and they have been reported to be associated with some renal diseases. The aim of our research is to explore whether genetic variations in EGFR and TNF-α have influence on renal function under exposure to various metals. This cross-sectional study consisted of 376 metal industrial workers, 396 participants of Taiwan Biobank, and 231 volunteers of health examinations. We identified 23 single nucleotide polymorphisms (SNPs) on the EGFR gene and 6 SNPs on the TNF-α gene, and we also measured their plasma concentration of cobalt, copper, zinc, selenium, arsenic, and lead. Multiple regression analysis was applied to investigate the association between various SNPs, metals, and renal function. Our results revealed some protective and susceptible genotypes under occupational or environmental exposure to metals. The individuals carrying EGFR rs2280653 GG might have declined renal function under excessive exposure to selenium, and those with EGFR rs3823585 CC, rs12671550 CC, and rs4947986 GG genotypes might be susceptible to lead nephrotoxicity. We suggest the high-risk population to prevent renal diseases.

摘要

金属暴露可能与肾功能损害有关,但大多数研究都没有考虑遗传多态性对其的影响。表皮生长因子受体(EGFR)和肿瘤坏死因子-α(TNF-α)在肾脏血流动力学中发挥重要作用,它们与一些肾脏疾病有关。我们的研究旨在探讨 EGFR 和 TNF-α 基因的遗传变异在暴露于各种金属下对肾功能的影响。本横断面研究包括 376 名金属工业工人、396 名台湾生物银行参与者和 231 名健康检查志愿者。我们确定了 EGFR 基因上的 23 个单核苷酸多态性(SNP)和 TNF-α 基因上的 6 个 SNP,并测量了他们的血浆钴、铜、锌、硒、砷和铅浓度。多变量回归分析用于研究各种 SNP、金属和肾功能之间的关系。我们的研究结果揭示了一些在职业或环境金属暴露下具有保护或易感基因型的个体。携带 EGFR rs2280653 GG 基因型的个体可能会在过度暴露于硒的情况下肾功能下降,而携带 EGFR rs3823585 CC、rs12671550 CC 和 rs4947986 GG 基因型的个体可能更容易受到铅的肾毒性影响。我们建议高危人群预防肾脏疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6919/8431338/a037ac2b3344/ijerph-18-08965-g001.jpg

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