Genetic polymorphisms in CYP1A1, CYP2D6, UGT1A6, UGT1A7, and SULT1A1 genes and correlation with benzene exposure in a Chinese occupational population.
Metabolic enzymes involved in benzene activation or detoxification, including cytochrome P-450 1A1 (CYP1A1), cytochrome P-450 2D6 (CYP2D6), UDP-glucuronosyltransferase 1A6 (UGT1A6), UDP-glucuronosyltransferase1A7 (UGT1A7), and sulfotransferase 1A1 (SULT1A1), were studied for their roles in human susceptibility to benzene poisoning. All 304 subjects were investigated with a unitary questionnaire and their DNA was isolated from blood samples by a routine phenol-chloroform extraction. The study included 152 benzene poisoning patients, and 152 control workers occupationally exposed to benzene in South China. The genotypes were determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique with genomic DNA. No individuals had the CYP 2D6 c.212 G>A variant alleles in this study. There is no association between the UGT1A6 c.181 T>A, UGT1A7 c.208 Trp>Arg, and SULT1A1 c.638 G>A genotypes and increased risk of benzene-induced carcinogenesis. Although most of the CYP2D6 haplotypes did not show any significant difference, the CYP2D6 haplotype CYP2D6 c.188 C/C, C/T, and c.4268 C/C was significantly overrepresented in the case group (OR 4.02, 95% CI: 2.53-6.39) compared with in controls. Overall, our data suggested that individuals with CYP1A1 c.5639 T/T, CYP2D6 c.188 C/C, C/T, and CYP2D6 c.4268 C/C genotypes tend to be more susceptible to benzene toxicity.
Gu
Shou-Yong
SY
Department of Occupational Health, School of Public Health, Fudan University. Shanghai. People's Republic of China.
Zhang
Zhong-Bin
ZB
Wan
Jun-Xiang
JX
Jin
Xi-Peng
XP
Xia
Zhao-Lin
ZL
D000328:Adult; D015239:Arylsulfotransferase / Q000235:genetics; D001554:Benzene / Q000378:metabolism / Q000506:poisoning*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D016172:DNA Fingerprinting; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D016273:Occupational Exposure; D012150:Polymorphism, Restriction Fragment Length; D012997:Solvents / Q000378:metabolism / Q000506:poisoning*
D004798:Enzymes; D012997:Solvents; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D001554:Benzene