ArticleArthritis research & therapy2007
Association of the diplotype configuration at the N-acetyltransferase 2 gene with adverse events with co-trimoxazole in Japanese patients with systemic lupus erythematosus.
Article in Arthritis research & therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?Rheumatology international · 2021Pooled it
- The association between NAT2 acetylator status and adverse drug reactions of sulfasalazine: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
- Population pharmacokinetics and Monte Carlo-based dosing optimization of trimethoprim-sulfamethoxazole.Antimicrobial agents and chemotherapy · 2025Article
- Genotypic and phenotypic landscapes of 51 pharmacogenes derived from whole-genome sequencing in a Thai population.PloS one · 2022Article
- NAT2 Gene rs1041983 is Associated with Anti-Tuberculosis Drug Induced Hepatotoxicity Among Pediatric Tuberculosis in Bandung, Indonesia.The application of clinical genetics · 2021Article
- Functional Characterization of the Effects ofFrontiers in genetics · 2021Article
- Case Study 10: A Case to Investigate Acetyl Transferase Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Genetic variation in aryl N-acetyltransferase results in significant differences in the pharmacokinetic and safety profiles of amifampridine (3,4-diaminopyridine) phosphate.Pharmacology research & perspectives · 2015Article
- PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2.Pharmacogenetics and genomics · 2014Review
- Evaluation of polymorphisms in the sulfonamide detoxification genes NAT2, CYB5A, and CYB5R3 in patients with sulfonamide hypersensitivity.Pharmacogenetics and genomics · 2012Article
- Influence of NAT2 polymorphisms on sulfamethoxazole pharmacokinetics in renal transplant recipients.Antimicrobial agents and chemotherapy · 2012Article
- Genetic polymorphisms of CYP2D6 oxidation in patients with systemic sclerosis.European journal of clinical pharmacology · 2009Article
- Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature.Journal of human genetics · 2008Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although co-trimoxazole (trimethoprim-sulphamethoxazole) is an effective drug for prophylaxis against and treatment of Pneumocystis pneumonia, patients often experience adverse events with this combination, even at prophylactic doses. 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 NAT2 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 NAT2*4 haplotype (5/7 [71.4%]) than in those with at least one NAT2*4 haplotype (13/47 [27.7%]; P = 0.034; relative risk = 2.58, 95% confidence interval = 1.34-4.99). In the case-control study the proportion of patients without NAT2*4 was significantly higher among those with severe adverse events (3/5 [60%]) than those without severe adverse events (6/52 [11.5%]; P = 0.024; odds ratio = 11.5, 95% confidence interval = 1.59-73.39). We conclude that lack of NAT2*4 haplotype is associated with adverse events with co-trimoxazole in Japanese patients with SLE.
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