Genetic polymorphisms of alcohol inducible CYP2E1 in Turkish population

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


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Molecular dynamics simulations and coupled nucleotide substitution experiments indicate the nature of A center dot A base pairing and a putative structure of the coralyne-induced homo-adenine duplex
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Coralyne is an alkaloid drug that binds homo-adenine DNA (and RNA) oligonucleotides more tightly than it does Watson-Crick DNA. Hud's laboratory has shown that poly(dA) in the presence of coralyne forms an anti-parallel duplex, however attempts to determine the structure by NMR spectroscopy and X-ray crystallography have been unsuccessful. Assuming adenine-adenine hydrogen bonding between the two poly(dA) strands, we constructed 40 hypothetical homo-(dA) anti-parallel duplexes and docked coralyne into the s...
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Baydar, Gözde; Kocabıyık, Semra; Department of Biotechnology (2006)
In this study, we have characterized some biochemical and electrophoretic features of recombinant 20S Proteasome from a thermoacidophilic archaeon Thermoplasma volcanium. As revealed by SDS-PAGE the 20S Proteasome was composed of two subunits, ?- and β- subunits with estimated molecular masses of 24 kDa and 23 kDa, respectively. The highest chymotryptic activity was observed over an alkaline pH range (pH 8.0 ا pH 9.0) and the optimum temperature for the activity was determined as 85oC. The heat stability of...
Citation Formats
G. Ulusoy, “Genetic polymorphisms of alcohol inducible CYP2E1 in Turkish population,” M.S. - Master of Science, Middle East Technical University, 2004.