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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
metadata.dc.subject.mesh: Adult
Case-Control Studies
Genome-Wide Association Study
HLA-B Antigens
HLA-DQ beta-Chains
Middle Aged
Issue Date: 28-Sep-2017
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 HLA-B, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69) P = 2.55 × 10-8 ). We HLA-sequenced a second cohort consisting of 40 cases and 142 treated controls, and confirmed significant associations with HLA-B*08:01, OR = 2.25 (95% CI (1.02, 4.97) P = 0.0439), in particular the HLA-B*08:01 haplotype HLA-DQB1*02:01-DRB1*03:01-B*08:01-C*07:01, OR = 3.79 (95% CI (1.63, 8.80) P = 0.0019), and with HLA-A*31:01, OR = 4.81 (95% CI (1.52, 15.26) P = 0.0077). The number needed to test for HLA-B*08:01 and HLA-A*31:01 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 HLA-B*08:01 or HLA-A*31:01.
metadata.dc.identifier.doi: 10.1002/cpt.805
Appears in Collections:Producción 2020

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