Acetylation phenotypes and biological variation in a French Caucasian population.
Factors affecting the caffeine acetylation phenotype were investigated in a French Caucasian population of 150 unrelated supposedly healthy subjects, aged 18 to 63 years. This population, including 75 men and 75 women, was used to determine whether the acetylation polymorphism is related to environmental influences such as smoking habits, intake of alcohol, use of oral contraceptives, use of certain drugs. The acetylation phenotype was assessed from the molar ratio of two caffeine metabolites: 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine. For values less than 0.85, the subjects were classified as poor acetylators (frequency, mean +/- SD: 61.3 +/- 7.9%) in this study. Dose recoveries of 5-acetylamino-6-formylamino-3-methyluracil (mean +/- SD) were 1.26 +/- 0.85% and 3.58 +/- 1.64% in slow and rapid acetylators, respectively. The recovery (mean +/- SD) of 1-methylxanthine in the 3 hour-urine was 2.86 +/- 1.51% in slow acetylators and 2.36 +/- 1.27% in rapid acetylators. The mean value (and SD) of the molar ratio was 0.437 (0.177) and 1.669 (0.651) for slow and rapid acetylators. Three other metabolite ratios can also provide an acetylation index: 5-acetylamino-6-formylamino-3-methyluracil/5-acetylamino-6-formylamino-3 - methyluracil + 1-methylxanthine + 1-methyluric acid; 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine + 1-methyluric acid + 1,7-dimethyluric acid; and 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine + 1-methyluric acid + 1,7-dimethyluric acid + 1,7-dimethylxanthine with a bimodal distribution for the former and a trimodal distribution for the two latter ratios, both showing about 95% concordance with the 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine ratio. Age did not influence the excretion of caffeine and its five major metabolites. A marked influence of sex was observed only on the unchanged caffeine excretion, and the effect was greater in slow acetylators than in rapid acetylators. The 5-acetylamino-6-formylamino-3-methyluracil excretion was about three times higher in rapid acetylators than in slow acetylators in both sexes.
Pontes
Z B
ZB
Centre de Médecine Préventive, Vandoeuvre-les-Nancy, France.
Vincent-Viry
M
M
Gueguen
R
R
Galteau
M M
MM
Siest
G
G
D000107:Acetylation / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002110:Caffeine / Q000378:metabolism*; D005260:Female; D005602:France; D005787:Gene Frequency; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012737:Sex Factors; D044465:White People / Q000235:genetics
D002110:Caffeine