Relationships among CYP2B6 genetic variants and serum levels of multiple polychlorinated biphenyls and hydroxylated metabolites in a Japanese population

IF 12.2 1区环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL

Journal of Hazardous Materials Pub Date : 2024-12-20 DOI:10.1016/j.jhazmat.2024.136953

Zhaoqing Lyu , Hatasu Kobayashi , Kodai Iwase , Koichi Haraguchi , Yukiko Fujii , Kouji H. Harada

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引用次数: 0

Abstract

Production of polychlorinated biphenyls (PCBs) has been banned since 2001 but health risks from exposure persist. PCBs are metabolized by cytochrome P450 enzymes, including CYP2B6. However, the link between CYP2B6 gene polymorphisms and PCB metabolisms is poorly characterized. This study investigated the relationships among serum levels of major indicator PCBs and hydroxylated PCBs (OH-PCBs), which are PCB metabolites, and polymorphisms in CYP2B6. Blood samples (n = 129) were analyzed for single nucleotide polymorphisms in CYP2B6 (p.Q172H and p.K262R), and the corresponding haplotypes (*1, *4, *6) were determined. Concentrations of PCBs and OH-PCBs were determined using gas chromatography and mass spectrometer. Congener-specific variations in PCB metabolism were associated with different CYP2B6 genotypes, particularly * 1/* 4 (hypothesized to increased expression) and * 6/* 6 (hypothesized to decreased expression). For certain PCBs, the * 1/* 4 genotype was linked to increased metabolite-to-parent compound ratios, while * 6/* 6 was associated with decreased ratios, as observed for PCB146 (β = 0.192, 95 % CI: [0.100, 0.283], p < 0.0001 for *1/*4; β = −0.235, 95 % CI: [–0.366, –0.105], p = 0.001 for *6/*6). However, other PCBs, such as PCB170 and PCB183, exhibited opposite or more complex patterns. Our findings indicate intricate effects of CYP2B6 gene polymorphisms on PCB metabolism and highlight the potential for genotype-specific risks in PCB-related toxicity.

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CYP2B6基因变异与日本人群血清中多种多氯联苯和羟基化代谢物水平的关系

自2001年以来，多氯联苯（PCBs）的生产已被禁止，但接触多氯联苯带来的健康风险仍然存在。多氯联苯通过细胞色素P450酶代谢，包括CYP2B6。然而，CYP2B6基因多态性与多氯联苯代谢之间的联系尚不清楚。本研究探讨了主要指标多氯联苯（PCB）、多氯联苯代谢物羟基化多氯联苯（oh -PCB）的血清水平与CYP2B6基因多态性的关系。分析血样（n=129） CYP2B6单核苷酸多态性（p.Q172H和p.K262R），并确定相应的单倍型（*1,*4,*6）。采用气相色谱法和质谱法测定多氯联苯和oh -多氯联苯的浓度。PCB代谢的同源特异性变异与不同的CYP2B6基因型有关，特别是*1/*4（假设表达增加）和*6/*6（假设表达减少）。对于某些多氯联苯，*1/*4基因型与代谢物-亲本复合比率增加有关，而*6/*6基因型与代谢物-亲本复合比率降低有关，如PCB146 (β = 0.192, 95% CI: [0.100, 0.283], p <；*1/*4为0.0001；β=−0.235,95%置信区间CI: -0.366, -0.105, p = 0.001 * 6 / * 6)。而其他pcb，如PCB170和PCB183，则表现出相反或更复杂的模式。我们的研究结果表明CYP2B6基因多态性对多氯联苯代谢的复杂影响，并强调了多氯联苯相关毒性中基因型特异性风险的潜在可能性。对环境的影响多氯联苯在环境和人体中持续存在，对健康构成潜在威胁。除了暴露源和暴露水平外，由于消除动力学的不同，人群中多氯联苯的血清水平也有很大差异。细胞色素P450被认为是PCB代谢的关键酶。本研究表明，CYP2B6变异，特别是*1/*4（表达增加）和*6/*6（表达减少）与血清中不同的同系物组成有关。此外，*1/*4基因型与几种多氯联苯的代谢物与亲本化合物比率增加有关，表明CYP2B6在其代谢中可能具有重要作用。这项研究提供了第一个证据，表明人类CYP2B6变异可能导致人群对多种多氯联苯代谢物的易感性。

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来源期刊

Journal of Hazardous Materials 工程技术-工程：环境

CiteScore

25.40

自引率

5.90%

发文量

3059

审稿时长

58 days

期刊介绍： The Journal of Hazardous Materials serves as a global platform for promoting cutting-edge research in the field of Environmental Science and Engineering. Our publication features a wide range of articles, including full-length research papers, review articles, and perspectives, with the aim of enhancing our understanding of the dangers and risks associated with various materials concerning public health and the environment. It is important to note that the term "environmental contaminants" refers specifically to substances that pose hazardous effects through contamination, while excluding those that do not have such impacts on the environment or human health. Moreover, we emphasize the distinction between wastes and hazardous materials in order to provide further clarity on the scope of the journal. We have a keen interest in exploring specific compounds and microbial agents that have adverse effects on the environment.