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., ...Daha Fazla

PHARMACOGENOMICS, cilt.10, sa.5, ss.769-778, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10 Sayı: 5
  • Basım Tarihi: 2009
  • Doi Numarası: 10.2217/pgs.09.22
  • Dergi Adı: PHARMACOGENOMICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.769-778
  • Anahtar Kelimeler: 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 Üniversitesi Adresli: Hayır

Özet

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.

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.