Cytochrome P450 2A6 phenotyping based on dietary caffeine intake in a Japanese population of non-smokers

Drug Metab Lett. 2012 Jun 1;6(2):67-72.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Caffeine / administration & dosage
  • Caffeine / metabolism*
  • Cytochrome P-450 CYP2A6
  • Female
  • Gene Deletion
  • Genotype
  • Humans
  • Japan
  • Male
  • Phenotype
  • Pilot Projects
  • Theophylline / urine*
  • Uric Acid / analogs & derivatives*
  • Uric Acid / urine
  • Xanthines / urine*
  • Young Adult

Substances

  • Xanthines
  • Uric Acid
  • Caffeine
  • 1-methylxanthine
  • Theophylline
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6
  • 1,7-dimethylxanthine
  • 1,7-dimethyluric acid