Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population.
OBJECTIVE
To study the variation in CYP1A2 activity in relation to smoking, gender, age and CYP1A2 polymorphisms.


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.


CONCLUSIONS
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.
Gunes
Arzu
A
Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden. Arzu.Gunes@medsci.uu.se
Ozbey
Gul
G
Vural
Elif Hilal
EH
Uluoglu
Canan
C
Scordo
Maria Gabriella
MG
Zengil
Hakan
H
Dahl
Marja-Liisa
ML
D000367:Age Factors; D002110:Caffeine / Q000097:blood; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D017384:Sequence Deletion; D012907:Smoking / Q000097:blood / Q000235:genetics*; D013806:Theophylline / Q000097:blood; D014421:Turkey
D002110:Caffeine; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine