2026-09-01T23:20:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/173352024-09-21T18:09:50Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
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
2024-01-23T20:13:08Z
2024-01-23T20:13:08Z
2017-09-28
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
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.
eng
Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus.
research article