Tsai Pei Chien, Huang Wenya, Lee Yeu-Chin, Chan Shih Huang, Guo Yueliang Leon
Department of Occupational and Environment Health, National Cheng Kung University, Tainan 701, Taiwan, ROC.
Chemosphere. 2006 May;63(8):1410-8. doi: 10.1016/j.chemosphere.2005.08.012. Epub 2006 Apr 3.
Polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) are ubiquitous persistent pollutants in humans. Whether people with different genotypes are with different susceptibility to these chemicals are unknown. In a group of people highly exposed to PCBs/PCDFs, we tested the hypothesis that genotypic polymorphisms affected susceptibility for development of skin manifestations.
In 1979, approximately 2000 people in central Taiwan ingested cooking oil contaminated with PCBs/PCDFs. Skin disorder such as chloracne, abnormal nail, hyperkeratosis and skin allergy were found in PCBs/PCDFs exposed group. We recruited exposed and community background exposure subjects for blood testing and telephone-interview. Single nucleotide polymorphisms, AhR Arg554Lys, CYP1A1 Ile462Val, CYP1A1 T6235C, and GSTM1/T1 deletion, were determined. Occurrence of skin manifestations was compared among people with different genotypes while stratified by PCB exposure levels by logistic regression.
Data on exposure, medical history, and genotypes were obtained from 393 exposed and 181 background exposure groups. Skin manifestations including chloracne, allergy, abnormal nail, and hyperkeratosis were more prevalent in exposed people in a dose-related manner. Among highly exposed individuals, combined CYP1A1-MspI mutant genotype and GSTM1-null genotype were associated with increased risk of chloracne (odds ratio 2.8, 95% confidence interval 1.1-7.6). Among intermediately exposed individuals, GSTM1 null genotype was associated with skin allergy. AhR Arg554Lys genotype and GSTT1 null genotype were not related to susceptibility to skin manifestations in PCB/PCDF-exposed population.
CYP1A1 and GSTM1 genotypic polymorphisms might be related to the susceptibility to PCB/PCDF-induced skin manifestations.
多氯联苯（PCBs）和二苯并呋喃（PCDFs）是人类环境中普遍存在的持久性污染物。不同基因型的人对这些化学物质的易感性是否不同尚不清楚。在一组高度暴露于多氯联苯/二苯并呋喃的人群中，我们检验了基因多态性影响皮肤表现发生易感性的假设。
1979年，台湾中部约2000人摄入了被多氯联苯/二苯并呋喃污染的食用油。在多氯联苯/二苯并呋喃暴露组中发现了氯痤疮、指甲异常、角化过度和皮肤过敏等皮肤疾病。我们招募了暴露组和社区背景暴露组的受试者进行血液检测和电话访谈。测定了单核苷酸多态性，即芳烃受体（AhR）的Arg554Lys、细胞色素P450 1A1（CYP1A1）的Ile462Val、CYP1A1的T6235C以及谷胱甘肽S-转移酶M1（GSTM1）/T1缺失。通过逻辑回归分析，比较了不同基因型人群在按多氯联苯暴露水平分层时皮肤表现的发生率。
从393名暴露组和181名背景暴露组受试者中获得了暴露、病史和基因型数据。包括氯痤疮、过敏、指甲异常和角化过度在内的皮肤表现在暴露人群中更普遍，且呈剂量相关。在高度暴露个体中，CYP1A1-MspI突变基因型与GSTM1缺失基因型组合与氯痤疮风险增加相关（比值比2.8，95%置信区间1.1-7.6）。在中度暴露个体中，GSTM1缺失基因型与皮肤过敏相关。AhR Arg554Lys基因型和GSTT1缺失基因型与多氯联苯/二苯并呋喃暴露人群的皮肤表现易感性无关。
CYP1A1和GSTM1基因多态性可能与多氯联苯/二苯并呋喃诱导的皮肤表现易感性有关。
