The effect of NAT2 genotype and gender on the metabolism of caffeine in nonsmoking subjects.
OBJECTIVE
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.
Welfare
M R
MR
Department of Pharmacological Sciences and; Department of Medicine, Medical School, University of Newcastle, Newcastle upon Tyne, UK. m.r.welfare@ncl.ac.uk
Bassendine
M F
MF
Daly
A K
AK
D000293:Adolescent; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D012907:Smoking
D000697:Central Nervous System Stimulants; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human