title: A population and family study of N-acetyltransferase using caffeine urinary metabolites.
abstract: Population and family studies were undertaken to validate caffeine as a probe drug to establish the genetic status of rapid acetylators and slow acetylators. The acetylator status was established from the urinary metabolic ratio of 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine (AFMU/1X) after oral administration of caffeine. We confirmed a bimodal distribution (chi 2(1) = 229.48; p << 10(-9)) of the AFMU/1X ratio in 245 unrelated subjects. A third distribution did not significantly improve the fit to the data (chi 2(1) = 0.04; p = 0.84). Complex segregation analysis of 76 nuclear families confirmed the monogenic inheritance of N-acetyltransferase, with incomplete dominance of the rapid allele over the slow one. We observed a slight shift between the mean activities of heterozygous and homozygous rapid acetylators (t = 2.89; p < 0.01). However, the 30 obligate heterozygotes belonging to the 76 families were evenly distributed among the rapid acetylators and never located in a hypothetic intermediary group between slow acetylators and rapid acetylators.
authors.affiliation: Service de Pharmacologie Clinique, CHU Jean Minjoz, Besançon, France.
authors.forename: Y C
authors.initials: YC
authors.lastname: Bechtel
authors.forename: C
authors.initials: C
authors.lastname: Bonaiti-Pellie
authors.forename: N
authors.initials: N
authors.lastname: Poisson
authors.forename: J
authors.initials: J
authors.lastname: Magnette
authors.forename: P R
authors.initials: PR
authors.lastname: Bechtel
mesh_terms: D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D002110:Caffeine / Q000493:pharmacokinetics* / Q000652:urine; D005190:Family; D006579:Heterozygote; D006801:Humans; D015233:Models, Statistical; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives* / Q000652:urine; D014970:Xanthines / Q000652:urine*
chemical_list: D014970:Xanthines; D002110:Caffeine; D014498:Uracil; C053085:1-methylxanthine; C036692:5-acetylamino-6-formylamino-3-methyluracil; D001191:Arylamine N-Acetyltransferase