In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population.
OBJECTIVE
The main aim of the study was to investigate the distribution of cytochrome P450 2A6 (CYP2A6) and xanthine oxidase (XO) enzyme activities in the Serbian population. Secondly, we tested the influence of genetics (CYP2A6 polymorphism), sex, and cigarette smoking on both enzymes.


METHODS
One hundred forty healthy Serbian volunteers were genotyped for common CYP2A6 alleles. In 100 of them, CYP2A6 and XO activities were determined by the urinary 17U/17X and 1U/(1U + 1X) ratios, respectively, after oral administration of 100 mg caffeine as a probe.


RESULTS
A 21-fold variation in the 17U/17X ratio was observed (range: 0.49-10.28, mean = 1.65, 95% CI: 1.49-1.83). The urinary 1U/(1U + 1X) ratios displayed four-fold variation, ranging from 0.17 to 0.71 (mean = 0.43, 95% CI: 0.41-0.45). CYP2A6 alleles *1A, *1B1, *9, *4 and *1B1x2 were found with frequencies of 0.579, 0.307, 0.082, 0.029, and 0.004 respectively. CYP2A6*5 was not detected. CYP2A6 genotype influenced interindividual variability in CYP2A6 enzyme activity (P = 0.04). Cigarette smoking inhibited CYP2A6 enzyme activity (P = 0.02), but had no effect on activity of XO (P = 0.16).There was no significant difference between men and women in terms of CYP2A6 or XO activity.


CONCLUSIONS
Serbs displayed interindividual variations in CYP2A6 activity. CYP2A6 genotype and cigarette smoking, but not sex, influenced CYP2A6 enzyme activity. Unimodal distribution of XO enzyme activity in Serbs implies the absence of subjects with low enzyme activity in this population. XO activity is not influenced by sex or cigarette smoking.
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, 14186, Stockholm, Sweden.
Natasa
N
Djordjevic
Juan Antonio
JA
Carrillo
Guillermo
G
Gervasini
Slobodan
S
Jankovic
Eleni
E
Aklillu
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D055771:Serbia / Q000208:ethnology; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology / Q000235:genetics; D044465:White People / Q000235:genetics*; D014969:Xanthine Oxidase / Q000235:genetics* / Q000378:metabolism*
D002110:Caffeine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D014969:Xanthine Oxidase