RT Journal Article T1 Next-generation sequencing and genotype association studies reveal the association of HLA-DRB3*02:02 with delayed hypersensitivity to penicillins A1 Romano, Antonino A1 Oussalah, Abderrahim A1 Chery, Celine A1 Gueant-Rodriguez, Rosa-Maria A1 Gaeta, Francesco A1 Cornejo-Garcia, Jose-Antonio A1 Rouyer, Pierre A1 Josse, Thomas A1 Mayorga, Cristobalina A1 Torres, Maria-Jose A1 Gueant, Jean-Louis K1 amoxicillin K1 beta-lactams K1 drug allergy K1 genome-wide association K1 HLA-DRB3 K1 nonimmediate reactions K1 penicillins K1 Allergic reactions K1 Variants K1 Linkage K1 Domain AB Background Nonimmediate (delayed)-allergic reactions to penicillins are common and some of them can be life-threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci. Methods Using next-generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. Results The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37-23.32; p PB Wiley SN 0105-4538 YR 2021 FD 2021-11-14 LK https://hdl.handle.net/10668/24391 UL https://hdl.handle.net/10668/24391 LA en DS RISalud RD Apr 17, 2025