한국인에서 구강상피세포를 이용한 발암물질 대사효소의 유전자 다형성에 관한 연구

Abstract

Xenobiotic-metabolizing machinery contains two main types of enzymes: the phase I enzymes mediating oxidative metabolism, cytochrome P450 (CYPs) and phase II conjugating enzymes involved in detoxification, glutathione-S-transferase (GSTs). Genes that encode these enzymes are polymorphic, and such polymorphisms are associated with the susceptibility to the hazardous action of chemicals such as carcinogens in some individuals. Moreover, genetic polymorphisms of xenobiotic-metabolizing enzymes have been shown considerable ethnic differences in gene structure and allelic distribution. In this study, we investigated the polymorphic genotypes of CYP1A1 (MspI and exon 7 polymorphisms), CYP2E1 and GSTM1 from oral epithelial cells of 225 healthy Koreans collected by mouthwash method. The genomic DNA was purified by phenol-chloroform extraction and the genotypes of CYP1A1, CYP2E1 and GSTM1 were determined by polymerase chain reaction-based assay. CYP1A1 MspI genotypes m1/m1, m1/m2 and m2/m2 were found in 36.3%, 55.7% and 8.0% of healthy Koreans and exon 7 genotypes were 16.8% for ile/ile, 74.8% for ile/val and 8.4% for val/val. The frequency of CYP1A1 m1/m2 was higher in Koreans than Europeans as compared with the previous studies. CYP1A1 ile/val genotype in Koreans was found to be significantly high in comparison with Japanese as well as Europeans and Caucasian. The c1/c1, c1/c2 and c2/c2 genotypes of CYP2E1 were observed as 53.3%, 43.8% and 2.9%. The presence of c2 allele was significantly more frequent in Koreans (24.3%) than in Swedish (5.0%), European- American (1.0%) and African-American (4.0%). GSTM1 wild and null genotypes were found in 39.0% and 61.0%, respectively and this was not significantly different from other ethnic