Comparison of a new in-house and three published HLA-B∗15:02 screening methods for prevention of carbamazepine-induced severe drug reactions

Abstract

Currently, there are three published HLA-B∗15:02 screening methods for prevention of carbamazepine-induced severe drug reactions in Asian populations. To analyze available HLA-B∗15:02 screening methods, we compared four screening methods, including a multiplex PCR method, a nested PCR method, a LAMP method and our new in-house PCR-dot blot hybridization method. These methods were reviewed regarding their sensitivity, specificity, false positivity and technical considerations. Possible false positive (FP) alleles and genotypes were checked regarding the primers and probes designs, using the IMGT/HLA database. Expected FP rates in Asian populations were predicted using the Allele Frequencies Net Database. All methods had a sensitivity of more than 99.9%, although giving FP results to certain very rare alleles and genotypes. The multiplex PCR method was the only test that gave FP results to certain genotypes of HLA-B∗15:13, the allele which is prevalent in Southeast Asian populations. In conclusion, the nested PCR, LAMP and our in-house methods could be applied in various Asian populations, but the multiplex PCR, or any test with FP to HLA-B∗15:13, should be applied with caution in the Southeast Asian populations.