Influence of genetic polymorphisms of styrene-metabolizing enzymes and smoking habits on levels of urinary metabolites after occupational exposure to styrene.
Here we evaluate the influence of individual genetic polymorphisms of drug-metabolizing enzymes as well as body mass index (BMI) and lifestyle (smoking, alcohol consumption) on urinary metabolites after occupational exposure to styrene. Seventy-three workers exposed to styrene in a reinforced-plastics workplace were studied. The personal styrene exposure in the air and the urinary styrene metabolites mandelic acid and phenylglyoxylic acid were measured. The subjects' genetic polymorphisms in the genes that encode the styrene-metabolizing enzymes CYP2E1, CYP2B6, EPHX1, GSTM1, GSTT1 and GSTP1 were determined. Neither genotype nor lifestyle significantly affected urinary metabolites. There was, however, an interaction between the CYP2E1 genotype and smoking. Among non-smokers, urinary styrene metabolites were significantly decreased in subjects with c1/c1 alleles of CYP2E1 as compared with those with the c1/c2 genotype. There was no significant difference in urinary metabolites among smokers. When the combined influence of the CYP2B6 genotype and the predicted activity of EPHX1 were examined, urinary metabolites in subjects with low enzyme activity were lower than in those with medium or high activity after high styrene exposure (>or=50 ppm). The results suggest that genetic susceptibility and lifestyle should be considered in biological monitoring of exposure to styrene.
Ma
Mingyue
M
Department of Public Health, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Sapporo, Hokkaido 060-8638, Japan. mamingy@med.hokudai.ac.jp
Umemura
Tomohiro
T
Mori
Yuko
Y
Gong
Yingyan
Y
Saijo
Yasuaki
Y
Sata
Fumihiro
F
Kawai
Toshio
T
Kishi
Reiko
R
D000328:Adult; D000428:Alcohol Drinking / Q000652:urine; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D015992:Body Mass Index; D065702:Cytochrome P-450 CYP2B6; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006038:Glyoxylates / Q000652:urine*; D006801:Humans; D008297:Male; D008333:Mandelic Acids / Q000652:urine*; D016273:Occupational Exposure / Q000009:adverse effects; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012907:Smoking / Q000652:urine; D020058:Styrene / Q000378:metabolism* / Q000506:poisoning*
D001189:Aryl Hydrocarbon Hydroxylases; D065702:Cytochrome P-450 CYP2B6; D019392:Cytochrome P-450 CYP2E1; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006038:Glyoxylates; D008333:Mandelic Acids; D010089:Oxidoreductases, N-Demethylating; D020058:Styrene; C012482:phenylglyoxylic acid; C585599:CYP2B6 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C037938:mandelic acid