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With the aim being to achieve individual optimization of co-trimoxazole therapy in patients with systemic lupus erythematosus (SLE), we investigated genetic polymorphisms in the<jats:italic>NAT2<\/jats:italic>gene (which encodes the metabolizing enzyme of sulphamethoxazole). Of 166 patients with SLE, 54 patients who were hospitalized and who received prophylactic doses of co-trimoxazole were included in the cohort study. Adverse events occurred in 18 patients; only two experienced severe adverse events that lead to discontinuation of the drug. These two patients and three additional ones with severe adverse events (from other institutions) were added to form a cohort sample and were analyzed in a case-control study. Genotype was determined using TaqMan methods, and haplotype was inferred using the maximum-likelihood method. In the cohort study, adverse events occurred more frequently in those without the<jats:italic>NAT2*4<\/jats:italic>haplotype (5\/7 [71.4%]) than in those with at least one<jats:italic>NAT2*4<\/jats:italic>haplotype (13\/47 [27.7%];<jats:italic>P<\/jats:italic>= 0.034; relative risk = 2.58, 95% confidence interval = 1.34\u20134.99). In the case-control study the proportion of patients without<jats:italic>NAT2*4<\/jats:italic>was significantly higher among those with severe adverse events (3\/5 [60%]) than those without severe adverse events (6\/52 [11.5%];<jats:italic>P<\/jats:italic>= 0.024; odds ratio = 11.5, 95% confidence interval = 1.59\u201373.39). We conclude that lack of<jats:italic>NAT2*4<\/jats:italic>haplotype is associated with adverse events with co-trimoxazole in Japanese patients with SLE.<\/jats:p>","DOI":"10.1186\/ar2134","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T07:03:35Z","timestamp":1172905415000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Association of the diplotype configuration at the N-acetyltransferase 2 gene with adverse events with co-trimoxazole in Japanese patients with systemic lupus erythematosus"],"prefix":"10.1186","volume":"9","author":[{"given":"Makoto","family":"Soejima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Sugiura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Katsumata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kae","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadayuki","family":"Mitamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Mimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Kamatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,3,3]]},"reference":[{"key":"1998_CR1","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1056\/NEJM199503163321101","volume":"332","author":"SA Bozzette","year":"1995","unstructured":"Bozzette SA, Finkelstein DM, Spector SA, Frame P, Powderly WG, He W, Phillips L, Craven D, van der Horst C, Feinberg J: A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. 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