Comparison of N-acetyltransferase-2 enzyme genotype-phenotype and xanthine oxidase enzyme activity between Swedes and Koreans

J Clin Pharmacol. 2012 Oct;52(10):1527-34. doi: 10.1177/0091270011420261. Epub 2011 Nov 21.

Abstract

The aim of this study was to compare xanthine oxidase (XO) and N-acetyltransferase-2 (NAT2) genotype and phenotype between Swedes (n = 113) and Koreans (n = 150), as well as to investigate the effect of sex, smoking, age, and oral contraceptive (OC) use on enzyme activities, using caffeine as a probe. XO and NAT2 activities were estimated by 1U/(1U+1X) and AFMU/(AFMU+1X+1U) urinary ratios, respectively. Participants were genotyped for 191G>A, 341T>C, 590G>A, and 857G>A NAT2 polymorphisms. There was no significant difference in XO activity between Swedes and Koreans. In Swedes, higher XO activity was observed in women (P < .003). There were significant differences in NAT2 genotype and phenotype between Swedes and Koreans. Koreans display significantly higher frequency of NAT2 fast acetylator genotype (89%), whereas the slow acetylator genotype is predominant (62%) in Swedes (P < .0001). Significantly higher NAT2 activity was observed in Koreans compared to Swedes (P < .0001). Having the same NAT2 fast acetylator genotype, Koreans display higher enzyme activity than Swedes (P < .004). OC use significantly increased NAT2 activity in Swedish women. In conclusion, Koreans display higher NAT2 activity than Swedes regardless of NAT2 genotype. Ethnicity, OC use, and genotype determine NAT2 activity, whereas sex is the only determinant of XO activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arylamine N-Acetyltransferase / genetics*
  • Asian Continental Ancestry Group* / genetics
  • Caffeine / pharmacokinetics
  • Contraceptives, Oral / pharmacology
  • European Continental Ancestry Group* / genetics
  • Genotype
  • Humans
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Sex Factors
  • Uracil / analogs & derivatives
  • Uracil / urine
  • Uric Acid / analogs & derivatives
  • Uric Acid / urine
  • Xanthine Oxidase / metabolism*
  • Xanthines / urine

Substances

  • Contraceptives, Oral
  • Xanthines
  • Uric Acid
  • 1-methyluric acid
  • Caffeine
  • Uracil
  • 1-methylxanthine
  • 5-acetylamino-6-formylamino-3-methyluracil
  • Xanthine Oxidase
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human