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

• Authors: Necat Yılmaz , Ayşe Bınnur Erbağcı , A Şükrü Aynacioğlu
• Languages of publication: EN

Abstracts

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 electrochemiluminescence 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.

Keywords

EN

CYP2C9 polymorphism; Anatolia; cytokines; tumour markers

• Journal: Acta Biochimica Polonica
• Year: 2001
• Volume: 48
• Issue: 3
• Pages: 775-782

Dates

published

2001

received

2000-11-15

revised

2001-02-21

accepted

2001-04-30

Contributors

author

Necat Yılmaz

• Department of Biochemistry and Clinical Biochemistry, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey

author

Ayşe Bınnur Erbağcı

• Departments of Biochemistry and Clinical Biochemistry, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey

author

A Şükrü Aynacioğlu

• Department of Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey

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