Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
Sci Total Environ. 2022 Feb 10;807(Pt 1):150753. doi: 10.1016/j.scitotenv.2021.150753. Epub 2021 Oct 5.
Bisphenols and triclosan (TCS) are common endocrine disrupters (EDCs) that may induce oxidative stress. However, there is limited information as to whether these EDCs interact with genetic variants to modify the levels of oxidative stress on a genome-wide scale.
We first performed a genome-wide scan among a Chinese population and also measured three urinary EDCs, including bisphenol A (BPA), bisphenol F (BPF) and TCS, and three urinary oxidative stress markers [4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-iso-prostaglandin-F (8-isoPGF) and 8-hydroxy-deoxyguanosine (8-OHdG)]. Subsequently, we examined interactions between three urinary EDCs and nearly 4.6 million genetic variants for three urinary oxidative stress markers by the general linear model.
Urinary BPA, BPF and TCS were positively associated with HNE-MA, 8-isoPGF and 8-OHdG. Significant rs6855040 (4p15.32/between SNORA75B and QDPR)-BPA, rs1112943 (4q35.1/SNX25)-TCS interactions were associated with the 8-isoPGF levels (all P < 5 × 10). In addition, rs4656116 (1p22.3/CACL1), rs16958760 (17p11.2/between USP43 and DHRS7C) and rs11651078 (17p11.2/LOC339260) showed significant gene-TCS interactions with 8-OHdG (all P < 5 × 10). The gene-level analysis found significant interaction between SNX25 and TCS for 8-isoPGF levels (P < 2.12 × 10).
Our results identify several gene-EDCs interactions for oxidative stress, highlighting that EDCs may modify the effect of genetic variants on oxidative stress.
双酚 A（BPA）和三氯生（TCS）是常见的内分泌干扰物（EDCs），可能诱导氧化应激。然而，关于这些 EDC 是否与遗传变异相互作用，从而在全基因组范围内改变氧化应激水平，相关信息十分有限。
我们首先在中国人群中进行了全基因组扫描，同时测量了三种尿内分泌干扰物，包括双酚 A（BPA）、双酚 F（BPF）和三氯生，以及三种尿氧化应激标志物[4-羟基-2-壬烯醛-巯基尿酸（HNE-MA）、8-异前列腺素 F（8-isoPGF）和 8-羟基脱氧鸟苷（8-OHdG）]。随后，我们通过一般线性模型，检测了三种尿内分泌干扰物与近 460 万个遗传变异之间对三种尿氧化应激标志物的相互作用。
尿 BPA、BPF 和 TCS 与 HNE-MA、8-isoPGF 和 8-OHdG 呈正相关。rs6855040（4p15.32/SNORA75B 和 QDPR 之间）-BPA、rs1112943（4q35.1/SNX25-TCS）相互作用与 8-isoPGF 水平相关（所有 P 值均<5×10）。此外，rs4656116（1p22.3/CACL1）、rs16958760（17p11.2/USP43 和 DHRS7C 之间）和 rs11651078（17p11.2/LOC339260）与 8-OHdG 表现出显著的基因-TCS 相互作用（所有 P 值均<5×10）。基因水平分析发现，SNX25 与 TCS 之间存在 8-isoPGF 水平的显著相互作用（P 值<2.12×10）。
本研究发现了几种氧化应激的基因-EDC 相互作用，提示 EDC 可能改变遗传变异对氧化应激的影响。
