The effects of two genetically associated polymorphisms [cl allele: Pstl -, Rsal +; c2 allele: Pstl +, Rsal - ] in the 5 -flanking region on the regulation and expression of the human CYP2E1 gene were investigated. DNase I footprinting and CAT activity analyses using various deletion mutants constructed with DNA segments from genotype A (cl/cl) or C (c2/c2) and SV40 or an endogenous promoter showed that the Rsal polymorphism affects the binding of a transcription factor and the transcriptional activation of CYP2E1, while the Pstl polymorphism has little effect. The correlation between the genotypes and expression levels of CYP2E1 mRNA were examined in peripheral lymphocytes of 86 individuals by RT-PCR, the alcohol consumption by the subjects being taken into account. In non-drinkers, the mean ratio of the expression of CYP2E1 mRNA to that of GAPDH mRNA in genotype B (cl/c2) was 1.7-fold higher than that in genotype A (0.05 < p < 0.10). As compared to non-drinkers with genotype A, subjects with genotype B who drank alcohol on a daily basis expressed about 2.0-fold higher levels of CYP2E1 mRNA (p<0.01). These results indicate that a Rsal polymorphism in the 5-flanking region of CYP2E1 may lead to inter-individual differences in CYP2El-mediated microsomal drug oxidation activities, including oxidation of -nitrosamines.
|Number of pages||6|
|Journal||Journal of biochemistry|
|Publication status||Published - 1994 Aug|
- CAT assay
- Transcriptional regulation.
ASJC Scopus subject areas
- Molecular Biology