2026-09-01T23:20:47Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/173352024-09-21T18:09:50Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Wadelius, Mia author Eriksson, Niclas author Kreutz, Reinhold author Bondon-Guitton, Emmanuelle author Ibañez, Luisa author Carvajal, Alfonso author Lucena, M Isabel author Sancho Ponce, Esther author Molokhia, Mariam author Martin, Javier author Axelsson, Tomas author Kohnke, Hugo author Yue, Qun-Ying author Magnusson, Patrik K E author Bengtsson, Mats author Hallberg, Pär author EuDAC author 2017-09-28 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. 10.1002/cpt.805 1532-6535 Clinical pharmacology and therapeutics http://hdl.handle.net/10668/11462 28762467 http://hdl.handle.net/20.500.12105/17335 Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus.