Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene

• Published in: Journal of rheumatology 2002-12, Vol.29 (12), p.2492
• Main Authors: Tanaka, Eiichi, Taniguchi, Atsuo, Urano, Wako, Nakajima, Hiroshi, Matsuda, Yuko, Kitamura, Yutaka, Saito, Masayuki, Yamanaka, Hisashi, Saito, Terunobu, Kamatani, Naoyuki
• Format: Article
• Language: English
• Subjects: Acetylation; Antirheumatic Agents - adverse effects; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - enzymology; Arthritis, Rheumatoid - genetics; Arylamine N-Acetyltransferase - genetics; Female; Haplotypes - genetics; Humans; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sulfasalazine - adverse effects
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: N-acetyltransferase 2 (NAT2) is a key enzyme for the acetylation of sulfasalazine (SSZ). We examine whether there was a correlation between diplotype configurations (combinations of 2 haplotypes for a subject) at the NAT2 gene and the adverse effects of SSZ used for the treatment of rheumatoid arthritis (RA). METHODS: The findings from 144 patients with RA who had been treated with SSZ were collected from our outpatient department and used for a retrospective study. Haplotype analysis was performed by the maximum-likelihood estimation based on the EM algorithm using the obtained polymorphism data. RESULTS: Sixteen patients (11.1%) had experienced adverse effects from SSZ, the most common being allergic reactions including rash and fever. The slow acetylators who had no NAT2*4 haplotype had experienced adverse effects more frequently (62.5%) than the fast acetylators who had at least one NAT2*4 haplotype (8.1%) (p < 0.001, OR 7.73, 95% CI 3.54-16.86). In 25% of the slow acetylators, the adverse effects were so severe that they were hospitalized. CONCLUSION: Genotyping the NAT2 gene followed by estimation of diplotype configuration before administration of SSZ is likely to reduce the frequency of adverse effects in Japanese patients with RA.