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 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 10 Issue: 5
  • Publication Date: 2009
  • Doi Number: 10.2217/pgs.09.22
  • Journal Name: PHARMACOGENOMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • 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
  • Akdeniz University Affiliated: No

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.

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 (-38606>A, -31136>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 (-38606, -31136, -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 -1630>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.