Nicoletti, PaolaCarr, Daniel FBarrett, SarahMcEvoy, LaurenceFriedmann, Peter SShear, Neil HNelson, Matthew RChiriac, Anca MBlanca-Lopez, NataliaCornejo-Garcia, Jose AGaeta, FrancescoNakonechna, AllaTorres, Maria JCaruso, CristianoValluzzi, Rocco LFloratos, ArisShen, YufengPavlos, Rebecca KPhillips, Elizabeth JDemoly, PascalRomano, AntoninoBlanca, MiguelPirmohamed, Munir2023-02-092023-02-092020-10-05Nicoletti P, Carr DF, Barrett S, McEvoy L, Friedmann PS, Shear NH, et al. Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort. J Allergy Clin Immunol. 2021 May;147(5):1830-1837.e15http://hdl.handle.net/10668/16426β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE. We sought to identify genetic predisposing factors for immediate reactions to β-lactam antibiotics. Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort. Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10-14); this was in linkage disequilibrium with HLA-DRB1∗10:01 (odds ratio, 2.93; P = 5.4 × 10-7) and HLA-DQA1∗01:05 (odds ratio, 2.93, P = 5.4 × 10-7). Haplotype analysis identified that HLA-DRB1∗10:01 was a risk factor even without the HLA-DQA1∗01:05 allele. The association with HLA-DRB1∗10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1∗10:01 increased the risk of immediate hypersensitivity at a genome-wide level (odds ratio, 2.96; P = 4.1 × 10-9). No association with HLA-DRB1∗10:01 was identified in 268 patients with delayed hypersensitivity reactions to β-lactams. HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Type I hypersensitivityAllergyAnaphylaxisCephalosporinsPenicillinsPharmacogenomicsβ-lactamsAdultAnti-Bacterial AgentsCephalosporinsCohort StudiesDrug HypersensitivityFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHLA-DQ alpha-ChainsHLA-DRB1 ChainsHumansHypersensitivity, ImmediateMaleMiddle AgedPenicillinsPhenotypePolymorphism, Single Nucleotideresearch article33058932open accessCadenas HLA-DRB1Hipersensibilidad inmediataOportunidad relativaAntibacterianosEstudio de asociación del genoma completo10.1016/j.jaci.2020.10.0041097-6825PMC8100096http://www.jacionline.org/article/S0091674920314056/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100096/pdf