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Genetic polymorphisms of alcohol inducible CYP2E1 in Turkish population

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2004
Ulusoy, Gülen
Cytochrome P4502E1 (CYP2E1), the ethanol-inducible isoform of cytochrome P450 superfamily, catalyzes many low molecular weight endogenous and exogenous compounds, including ethanol, acetone, drugs like acetaminophen and chlorzoxazone, and industrial solvents like benzene and styrene, most of which are carcinogenic. Besides, it has a high capacity to produce reactive oxygen species. CYP2E1 is induced by ethanol and isoniazid, as well by some pathophysiological conditions like diabetes and starvation. CYP2E1 gene shows genetic polymorphisms which are thought to play a major role in interindividual variability in drug response and in susceptibility to chemical-induced diseases, like several types of cancers. It is well established that CYP2E1 polymorphisms vary markedly in frequency among different ethnic and racial groups. Therefore, in this study, the frequency of two important CYP2E1 polymorphisms; the single nucleotide polymorphisms C-1019T / G-1259C in 52-flanking region and T7678A poymorphism in intron 6, in Turkish population was investigated. For this purpose, whole blood samples were collected from 132 healthy volunteers representing Turkish population and genomic DNA for each subject was isolated in intact form. The genotypes were determined by PCR amplification of corresponding regions followed by restriction endonuclease RsaI, PstI (for C-1019T / G-1259C SNPs) and DraI (for T7678A SNP) digestions. The genotype frequencies, for C-1019T / G-1259C SNPs, which are in complete linkage disequilibrium, were investigated on 116 DNA samples, and determined as 97.4% for homozygous wild type (c1/c1), 2.6% for heterozygotes (c1/c2) and 0.0% for homozygous mutants (c2c2). The allele frequency of wild type allele (c1) was calculated as 98.7% and that of mutated allele (c2) as 1.3%. The genotype frequencies for T7678A SNP, investigated in 108 DNA samples were determined as