Genetic Polymorphisms in CYP1A1, CYP2D6, UGT1A6, UGT1A7, and SULT1A1 Genes and Correlation with Benzene Exposure in a Chinese Occupational Population

Abstract

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.

This study was supported by the National Natural Science Foundation of China (30271113) and China National Key Basic Research and Development Program (2002CB512902). We thank Duozhi Cao (Institute of Occupational Health attached to Maanshan Steel & Iron Group, Maanshan, Anhui, China), Weiwei Liu (Guangzhou Hospital for Occupational Diseases, Guangzhou, Guangdong, China), and Rong Ye and Jiru Guan (Hangzhou Center for Diseases Control and Prevention, Hangzhou, Zhejiang, China) for their contribution to field research and physical examination in this study.