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- Title
Sulfasalazine‐Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus.
- Authors
Wadelius, Mia; Eriksson, Niclas; Kreutz, Reinhold; Bondon‐guitton, Emmanuelle; Ibañez, Luisa; Carvajal, Alfonso; Lucena, M. Isabel; Sancho Ponce, Esther; Molokhia, Mariam; Martin, Javier; Axelsson, Tomas; Kohnke, Hugo; Yue, Qun‐ying; Magnusson, Patrik K. E.; Bengtsson, Mats; Hallberg, Pär; On Behalf Of Eudac
- Abstract
Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine, which is used to treat inflammatory joint and bowel disease. We performed a genome‐wide association study comprising 9,380,034 polymorphisms and 180 HLA alleles in 36 cases of sulfasalazine‐induced agranulocytosis and 5,170 population controls. Sulfasalazine‐induced agranulocytosis was significantly associated with the HLA region on chromosome 6. The top hit (rs9266634) was located close to <italic>HLA‐B</italic>, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69) <italic>P</italic> = 2.55 × 10−8). We HLA‐sequenced a second cohort consisting of 40 cases and 142 treated controls, and confirmed significant associations with <italic>HLA‐B*08:01</italic>, OR = 2.25 (95% CI (1.02, 4.97) <italic>P</italic> = 0.0439), in particular the <italic>HLA‐B*08:01</italic> haplotype <italic>HLA‐DQB1*02:01‐DRB1*03:01‐B*08:01‐C*07:01</italic>, OR = 3.79 (95% CI (1.63, 8.80) <italic>P</italic> = 0.0019), and with <italic>HLA‐A*31:01</italic>, OR = 4.81 (95% CI (1.52, 15.26) <italic>P</italic> = 0.0077). The number needed to test for <italic>HLA‐B*08:01</italic> and <italic>HLA‐A*31:01</italic> to avoid one case was estimated to be 1,500. We suggest that intensified monitoring or alternative treatment should be considered for known carriers of <italic>HLA‐B*08:01</italic> or <italic>HLA‐A*31:01</italic>.
- Subjects
AGRANULOCYTOSIS; HLA histocompatibility antigens; JOINT diseases; CHROMOSOMES; DRUG side effects; THERAPEUTICS
- Publication
Clinical Pharmacology & Therapeutics, 2018, Vol 103, Issue 5, p843
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1002/cpt.805