Genetic polymorphisms in CYP1A1 and GSTM1 predispose humans to PCBs/PCDFs-induced skin lesions.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
CYP1A1 and GSTM1 genotypic polymorphisms might be related to the susceptibility to PCB/PCDF-induced skin manifestations.
Department of Occupational and Environment Health, National Cheng Kung University, Tainan 701, Taiwan, ROC. pctsai@ms35.url.com.tw
Pei Chien
PC
Tsai
Wenya
W
Huang
Yeu-Chin
YC
Lee
Shih Huang
SH
Chan
Yueliang Leon
YL
Guo
D000328:Adult; D001572:Benzofurans / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D000072338:Dibenzofurans, Polychlorinated; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D005506:Food Contamination; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010938:Plant Oils; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011110:Polymorphism, Genetic; D012871:Skin Diseases / Q000139:chemically induced / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
D001572:Benzofurans; D019363:Cytochrome P-450 CYP1A1; D000072338:Dibenzofurans, Polychlorinated; D004785:Environmental Pollutants; D005982:Glutathione Transferase; D010938:Plant Oils; D011078:Polychlorinated Biphenyls