title: Cytochrome P450 2A6 phenotyping based on dietary caffeine intake in a Japanese population of non-smokers.
abstract: Phenotyping of cytochrome P450 2A6 (CYP2A6) was determined by assessing urinary caffeine metabolites in a Japanese population with a high frequency of CYP2A6 whole-gene deletion (CYP2A6*4). The levels of 1,7-dimethyluric acid (17U), 1-methylxanthine (1X), and 1,7-dimethylxanthine (17X) were measured in non-smokers whose CYP2A6 and NAT2 genotypes had been determined. Low 17U/1X ratios were observed in accumulated overnight urine samples of subjects genotyped as CYP2A6*4/*4 after caffeine treatment. The individual 17U/1X ratios in spot urine samples were almost constant before and 2-8 h after caffeine treatment, with or without prior abstention from dietary caffeine. The average 17U/1X ratios obtained from subjects with CYP2A6 *4/ *4 or CYP2A6 *1/ *4 genotypes were significantly lower than those from subjects with wild-type CYP2A6 *1/ *1 under dietary caffeine consumption. The present results suggest that impaired CYP2A6 function associated with CYP2A6 *4/ *4 could be determined using the 17U/1X ratios in spot urine samples under normal dietary caffeine consumption in Japanese non-smokers, without the need for additional caffeine administration or prior abstention from caffeine.
authors: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors: Miyuki
authors: M
authors: Kimura
authors: Makiko
authors: M
authors: Shimizu
authors: Kazuma
authors: K
authors: Kiyotani
authors: Kazuko
authors: K
authors: Nakagawa
authors: Tetsuya
authors: T
authors: Kamataki
authors: Hiroshi
authors: H
authors: Yamazaki
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002110:Caffeine / Q000008:administration & dosage / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D010641:Phenotype; D010865:Pilot Projects; D013806:Theophylline / Q000652:urine*; D014527:Uric Acid / Q000031:analogs & derivatives* / Q000652:urine; D014970:Xanthines / Q000652:urine*; D055815:Young Adult
chemical_list: D014970:Xanthines; D014527:Uric Acid; D002110:Caffeine; C053085:1-methylxanthine; D013806:Theophylline; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; C021183:1,7-dimethylxanthine; C053084:1,7-dimethyluric acid