A FUNCTIONAL GENETIC MARKER IN CYP2E1 GENE FOR LEUKEMIA AND BENZENE RELATED TOXICITY

摘要

The cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia. The purpose of this study was to selected the functional genetic markers of leukemia associated with carcinogens activated by CYP2E1 including benzene. We performed a case-control study to select the genetic markers of leukemia from six multiple SNP of CYP2E1 in Chinese Han population and evaluate the impact ofSNP variation in CYP2E1 gene function of the expression of mRNA on the human immortalized lymphocytes treated with 0.1% phenol The multiplex PCR technique based on adapter-ligation mediated allele-specific amplification (ALM- ASA) was used to detect multiple SNP genotypes and the real-time reverse transcription-polymerase chain reaction (RT - PCR) approaches was used to detect and estimate levelsof CYP2E1 mRNAs. SNP were found at -1531T＞A, -377T＞C, -298T＞A. A marked linkage disequilibrium was found among -1531 and -298 sites. Three haplotypes were constructed. Three SNP and haplotypes analysis showed the frequency of the -1531 T＞A mutant genotypes and hapfotype of -1531A/-298A was significantly less in cancer cases. Phenol treatmentof cells resultedin a increase in mRNA expression, comparedwith untreated cells. The SNP of CYP2E1 - 298TT induced the CYP2E1 mRNA to a higher expression than - 298 TC/ CC with significant by treated with phenol. The result demonstrated that haplotype of -1531A/-298A may be a functional protective genetic marker of benzene toxicity and leukemia.