The effect of NAT2 genotype and gender on the metabolism of caffeine in nonsmoking subjects

Br J Clin Pharmacol. 2000 Mar;49(3):240-3. doi: 10.1046/j.1365-2125.2000.00130.x.

Abstract

Aims: To establish whether gender or N-acetyltransferase 2 (NAT2) genotype influence the urinary 17 U+17X/137X ratio after dosing with caffeine.

Methods: Ninety-two nonsmoking individuals underwent caffeine phenotyping. NAT2 genotype was determined by the polymerase chain reaction followed by a restriction digest (PCR-RFLP).

Results: The median ratio for urinary 17 U+17X/137X was 6.7 (range 1.45-18. 65). 55% of subjects were slow acetylators. Gender did not affect the metabolic ratio or NAT2 genotype. Mean 17 U+17X/137X ratio differed between fast (6.75) and slow (8.69) acetylators (95% CI for the difference, 0.32-3.56).

Conclusions: The findings are further evidence that the 17 U+17X/137X urinary ratio is not a robust measure of CYP1A2 activity. A possible mechanism by which the ratio might be influenced by NAT2 genotype is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arylamine N-Acetyltransferase / genetics
  • Arylamine N-Acetyltransferase / metabolism*
  • Caffeine / metabolism*
  • Central Nervous System Stimulants / metabolism*
  • Cytochrome P-450 CYP1A2 / metabolism
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Sex Characteristics*
  • Smoking

Substances

  • Central Nervous System Stimulants
  • Caffeine
  • Cytochrome P-450 CYP1A2
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human