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.
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.
Authors: Ted R Mikuls; Tricia Levan; Karen A Gould; Fang Yu; Geoffrey M Thiele; Kimberly K Bynote; Doyt Conn; Beth L Jonas; Leigh F Callahan; Edwin Smith; Richard Brasington; Larry W Moreland; Richard Reynolds; Angelo Gaffo; S Louis Bridges Journal: Arthritis Rheum Date: 2012-03
Authors: K Skretkowicz; J Skretkowicz; B Gawrońska-Szklarz; W Górnik; M Rychlik-Sych; A Sysa-Jedrzejowska Journal: Eur J Clin Pharmacol Date: 2004-11-24 Impact factor: 2.953
Authors: Eckart Schnakenberg; Karl-Rainer Fabig; Martin Stanulla; Nils Strobl; Michael Lustig; Nathalie Fabig; Werner Schloot Journal: Environ Health Date: 2007-02-10 Impact factor: 5.984