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

摘要

Abstract Genetic risk factors could cause cutaneous adverse drug reactions ( cADR s) in patients after treatment with clarithromycin. This study explored the association of HLA class I genes with clarithromycin‐ cADR s 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 Schr?dinger 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‐ cADR s 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‐ cADR s in Han Chinese and serve as a useful biomarker for personalized medicine to prevent clarithromycin‐ cADR s.