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

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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.

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Chen, S. A., Zhang, L. R., Yang, F. P., Yang, L. L., Yang, Y., Chen, Z. H., … Luo, X. Q. (2018). HLA-A*02:07 Allele Associates with Clarithromycin-Induced Cutaneous Adverse Drug Reactions in Chinese Patients. Basic and Clinical Pharmacology and Toxicology, 123(3), 308–313. https://doi.org/10.1111/bcpt.13011

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