HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity

초록

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drugrelated morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide signi ficant at the 5 x 10( -8) signi ficance level. Cefaclor induced type I hypersensitivity was signi fi- cantly associated with HLA-DRB1*04:03 (OR 4.61 [95% CI 1.51 - 14.09], P < 0.002) and HLADRB1*14:54 (OR 3.86 [95% CI 1.09 - 13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1*04:03 and HLA-DRB1*14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further con firmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.

키워드