@article {Tanaka2492, author = {Eiichi Tanaka and Atsuo Taniguchi and Wako Urano and Hiroshi Nakajima and Yuko Matsuda and Yutaka Kitamura and Masayuki Saito and Hisashi Yamanaka and Terunobu Saito and Naoyuki Kamatani}, title = {Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene.}, volume = {29}, number = {12}, pages = {2492--2499}, year = {2002}, publisher = {The Journal of Rheumatology}, abstract = {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.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/29/12/2492}, eprint = {https://www.jrheum.org/content/29/12/2492.full.pdf}, journal = {The Journal of Rheumatology} }