Cytochrome P4502C9 genotype in Southeast Anatolia and possible relation with some serum tumour markers and cytokines

• Autorzy: Yilmaz N. , Erbagci A.B. , Aynacioglu A.S.
• Języki publikacji: EN

Abstrakty

EN

Substrates for CYP2C9 include fluoxetine, phenytoin, warfarin, losartam and nu­merous nonsteroidal anti-inflammatory drugs. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino-acid residues 144 Arg/Cys and 359 Ile/Leu of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, the frequency of this al­lele is, however, rather low. Consistently with the modulation of enzyme activity by ge­netic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. The polymorphic en­zyme CYP2C9 takes part in the metabolism of alkylating agents and polycyclic aro­matic hydrocarbons like benzo(a)pyrene, a carcinogen present in tobacco smoke. Al­though the impact of impaired enzyme activity in metabolism of carcinogens and procarcinogens has not been fully defined, an association of CYP2C9 variant alleles to DNA adduct levels in lung tissues as well as to lung cancer risk have been reported. In this study 64 healthy subjects (44M/22F) were analysed for CYP2C9 genotype with PCR-RFLP and for serum carcinoembryonic antigen (CEA), α-fetoprotein (AFP), CA 19-9, CA 15-3, ferritin, IL-6, IL-8 concentrations by chemiluminescence or electro- chemiluminescence methods. CYP2C9*1 was found to be the most prevalent allele and CYP2C9*1/CYP2C9*1 was the most frequent genotype represented in 64% of the population in southeastern Anatolia (Gaziantep). Although slight differences in serum tumour marker and cytokine concentrations were observed for CYP2C9 genotypes the differences were statistically insignificant (P > 0.05). This could be due to the complexity of the role of CYP2C9 in benzo(a)pyrene metabo­lism as well as from other contributing factors like interindividual variability of di­verse enzymes participating in the same metabolic pathway, unequal expression of the variant alleles and differences in exposure to carcinogens. However, determination of CYP2C9 phenotypes in a larger group of subjects might clarify these slight differences.

Słowa kluczowe

EN

interleukin; carcinoembryonic antigen; polymorphism; CYP2C9 protein; serum; cytokine; genotype; tumour marker; CYP2C9 substrate; cytochrome P450; alpha-fetoprotein

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2001
• Tom: 48
• Numer: 3
• Opis fizyczny: p.775-782

Twórcy

autor

Yilmaz N.

• University of Gaziantep, TR-27310 Gaziantep, Turkey

autor

Erbagci A.B.

autor

Aynacioglu A.S.

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