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Página principal > Artículos > Artículos publicados > Sulfasalazine-induced agranulocytosis is associated with the human leukocyte antigen locus |
Fecha: | 2018 |
Resumen: | 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. |
Ayudas: | Instituto de Salud Carlos III FIS10-02632 Instituto de Salud Carlos III FIS12-00378 |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Clinical Pharmacology and Therapeutics, Vol. 103, núm. 5 (May 2018) , p. 843-853, ISSN 1532-6535 |
Published Version 11 p, 416.9 KB |