HLA‐A*02:07 Allele Associates with Clarithromycin‐Induced Cutaneous Adverse Drug Reactions in Chinese Patients.

Abstract: Genetic risk factors could cause cutaneous adverse drug reactions (cADRs) in patients after treatment with clarithromycin. This study explored the association of HLA class I genes with clarithromycin‐cADRs in Han Chinese patients. A total of 12 clarithromycin‐cADR patients and 34 clarithromycin‐tolerant controls were recruited for the high‐resolution genotyping of HLA class I genes (HLA‐A, HLA‐B and HLA‐C). The population controls consisted of 283 Han Chinese retrieved from the MHC database for validated comparison. A molecular docking analysis of HLA‐A*02:07 protein and clarithromycin was conducted using glide module with Schrödinger Suite. Among all tested HLA alleles, the carrier frequencies of HLA‐A*02:07 (58% versus 5.9%, OR = 22.40, 95% CI = 3.58–139.98, p = 8.20 × 10E‐5, pc = 1.1 × 10E‐3) and HLA‐B*46:01 (50% versus 5.9%, OR = 16.00, 95% CI = 2.59–98.99, p = 0.002, pc = 0.03) were significantly higher in clarithromycin‐cADRs than in clarithromycin‐tolerant controls. However, when compared to population controls, only HLA‐A*02:07, and not HLA‐B*46:01, reached statistical significance (58% versus 15.5%, OR = 7.61, 95% CI = 2.31–25.04, p = 1.2 × 10E‐4, pc = 1.7 × 10E‐3). Furthermore, molecular docking data revealed that clarithromycin could bind to and interact with HLA‐A*02:07 in two possible binding situations. These data suggest that HLA‐A*02:07 might be a genetic risk factor for developing clarithromycin‐cADRs in Han Chinese and serve as a useful biomarker for personalized medicine to prevent clarithromycin‐cADRs. [ABSTRACT FROM AUTHOR]