Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population


Gunes A., Ozbey G., Vural E. H. , ULUOĞLU C., Scordo M. G. , Zengil H., ...More

Pharmacogenomics, vol.10, no.5, pp.769-778, 2009 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 10 Issue: 5
  • Publication Date: 2009
  • Doi Number: 10.2217/pgs.09.22
  • Title of Journal : Pharmacogenomics
  • Page Numbers: pp.769-778
  • Keywords: age, caffeine, CYP1A2, gender, pharmacogenetics, polymorphisms, smoking, XANTHINE-OXIDASE ACTIVITIES, IN-VIVO, ENVIRONMENTAL-FACTORS, CAFFEINE METABOLISM, JAPANESE POPULATION, TARDIVE-DYSKINESIA, 5'-FLANKING REGION, CHINESE POPULATION, ASSOCIATION, CLOZAPINE

Abstract

Aims: To study the variation in CYP1A2 activity in relation to smoking, gender, age and CYP1A2 polymorphisms. Materials & methods: CYP1A2 activity was determined by plasma paraxanthine:caffeine ratio (17X:137X) 4 h after the intake of a standardized cup of coffee in 146 Turkish healthy volunteers. Seven CYP1A2 polymorphisms (-3860G>A, -3113G>A, -2467del/T, -739T>G, -729C>T, -163C>A and 5347T>C) were analyzed. Results: The 17X:137X ratios were increased in smokers (p < 0.0001) and tended to be higher in men both among nonsmokers (p = 0.051) and smokers (p = 0.064). Age-related differences were observed only among nonsmoking women (p = 0.024). The -163C>A polymorphism correlated with 17X:137X ratios only in smokers (p = 0.006). Furthermore, increased 17X:137X ratios were observed in CYP1A2 haplotype H4 (-3860G, -3113G, -2467del, -739T, -729C, -163A and 5347T) carriers in the overall study population (p = 0.026). Multiple regression analyses including smoking, gender, -163C>A genotype and age revealed a significant influence of smoking (p < 0.0001) and gender (p = 0.002) in the overall study population. However, in nonsmokers only the influence of gender remained significant (p = 0.021), while in smokers the influence of the -163C>A genotype held the statistical significance (p = 0.019). The influence of haplotype H4 remained significant (p = 0.028) in the overall study population in similar analyses. Conclusion: Smoking has the strongest impact on CYP1A2 activity, while gender and haplotype H4 showed marginal effects. The influence of the -163C>A polymorphism on CYP1A2 activity in smokers suggests an effect on the inducibility of the enzyme. © 2009 Future Medicine Ltd.