Increased genotype frequency of N-acetyltransferase 2 slow acetylation in patients with rheumatoid arthritis

Clin Pharmacol Ther. 2002 Sep;72(3):319-25. doi: 10.1067/mcp.2002.126740.

Abstract

Objectives: Acetylation polymorphism can alter therapeutic responses and toxicity to certain xenobiotics and may also be a factor that influences a patient's susceptibility to certain diseases. We investigated whether patients with rheumatoid arthritis (RA) differed from healthy individuals with regard to genotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2).

Methods: NAT2 polymorphism was compared in 118 healthy subjects and 82 patients with RA. NAT2 alleles (*4, *5, *6, and *7) were determined by polymerase chain reaction-restriction fragment length polymorphism methods with deoxyribonucleic acid extracted from peripheral blood.

Results: A statistically significant increase in the proportion of homozygous slow acetylators with 2 mutated alleles (84.1%) was found among patients with RA in comparison with healthy subjects (52.5%; P <.0001). The risk of development of RA was almost 5-fold greater in slow acetylators than in fast acetylators (odds ratio, 4.79; 95% confidence interval, 2.28-10.21). There was no correlation between NAT2 polymorphism and presence of rheumatoid factor, extra-articular manifestations, and age at first occurrence of disease symptoms.

Conclusions: NAT2 slow acetylation genotype may be a risk factor of individual susceptibility to RA.

Publication types

  • Comparative Study

MeSH terms

  • Acetylation
  • Adolescent
  • Adult
  • Aged
  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / genetics*
  • Arylamine N-Acetyltransferase / genetics*
  • Arylamine N-Acetyltransferase / metabolism*
  • Chi-Square Distribution
  • Confidence Intervals
  • Female
  • Gene Frequency / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics

Substances

  • Arylamine N-Acetyltransferase
  • NAT2 protein, human