Racial and gender differences in N-acetyltransferase, xanthine oxidase, and CYP1A2 activities

• Published in: Clinical pharmacology and therapeutics Vol. 52; no. 6; p. 643
• Main Authors: Relling, M V, Lin, J S, Ayers, G D, Evans, W E
• Format: Journal Article
• Language: English
• Published: United States 01.12.1992
• Subjects: Adolescent; Adult; Aging - urine; Analysis of Variance; Arylamine N-Acetyltransferase - urine; Caffeine - metabolism; Child; Child, Preschool; Continental Population Groups; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme System - urine; Female; Humans; Male; Middle Aged; Oxidoreductases - urine; Reference Values; Sex Characteristics; Xanthine Oxidase - urine
• ISSN: 0009-9236
• DOI: 10.1038/clpt.1992.203

The urinary molar concentration ratios of several caffeine metabolites are indicators of specific drug metabolizing enzyme activities. The ratios of 5-acetyl-amino-6-formylamino-3-methyluracil (AFMU) to 1-methylxanthine (1X), AFMU to 1X plus 1-methyluric acid (1U), and AFMU to 1X + 1U + AFMU are indicative of N-acetyltransferase (NAT) activity; the ratios of 1U to 1X and 1U to 1U + 1X indicate xanthine oxidase activity; and the ratio of the sum of 7-demethylated metabolites (AFMU + 1X + 1U) to the precursor for all three compounds, paraxanthine (PX), is a putative indicator of CYP1A2 oxidative activity. Our objective was to discern whether there are race-, gender-, and age-related differences in these indexes of drug-metabolizing activity. In 342 normal healthy unrelated subjects, metabolites were measured in urine collected after administration of low-dose caffeine. By two-way analysis of variance, NAT activity was higher in black subjects than in white subjects when assessed as AFMU/(1U + 1X) or as AFMU/(AFMU + 1U + 1X) (p = 0.001 and p = 0.002, respectively), but less so by use of AFMU/1X (p = 0.08). Xanthine oxidase activity, as assessed by 1U/1X or as 1U/(1U + 1X), was lower in black subjects than in white subjects (p = 0.02 and p = 0.001, respectively) and was lower in males than in females (p = 0.001 for both ratios). Females had higher AFMU/1X ratios (p = 0.03) because of higher xanthine oxidase activity. In a model in which AFMU/1X was the dependent variable and race, sex, age, and an index of xanthine oxidase (1U/1X) were independent variables, only race and 1U/1X were significant determinants of this NAT index (p = 0.003 and p < 0.001, respectively). The CYP1A2 ratio was lower in black subjects (p = 0.036) and in females (p = 0.015). Racial and gender differences in xanthine oxidase activity render the AFMU/1X ratio less reliable as an assessment of NAT activity in a heterogeneous population compared with the AFMU/(1U + 1X) or AFMU/(AFMU + 1U + 1X) ratios. The observed racial and gender differences in NAT, xanthine oxidase, and CYP1A2 activities may have implications for racial and gender differences in drug effects and carcinogen biotransformation.