Association of the HLA-DRB3 locus with delayed hypersensitivity to penicillins in the Spanish population
In order to confirm the potential enrichment in the HLA-DRB3locus showed by the HLA NGS/NGS-based HLA typing of the 24 Italian patients, we performed a fine-mapping genetic association study to assess the per-variant and per-haplotype risk associations with genetic variants of the HLA-DRB3 genomic region in 98 Spanish patients with delayed hypersensitivity compared with 1,308 controls. The clinical and demographic characteristics of patients and controls are given insupplemental tables 6, 7 and 8 , respectively. The haplotype block is shown in Figure 1 . We found that a haplotype (ACAA ) from four genetic variants – rs9268835, rs6923504, rs6903608, and rs9268838 – was significantly associated with the risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06–1.92; P =0.001) (Table 3 ). In the per-variant analysis, two variants (rs9268835, rs9268838) of the four included in the ACAA haplotype were significantly associated with the risk of delayed hypersensitivity to penicillins, with a similar effect size (Table 4 ). We subsequently assessed the risk association of theACAA haplotype in 315 patients with immediate reactions compared with 1,308 controls. The haplotype and per-variant association studies revealed no significant associations with the ACAA haplotype or with the rs9268835 and rs9268838 variants (Tables 3 and 4 ).