Molecular identification of HLA-B75 serotype markers by qPCR: A more inclusive pharmacogenetic approach before carbamazepine prescription
Issued Date
2024-06-01
Resource Type
ISSN
17528054
eISSN
17528062
Scopus ID
2-s2.0-85196324110
Journal Title
Clinical and Translational Science
Volume
17
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical and Translational Science Vol.17 No.6 (2024)
Suggested Citation
Jaruthamsophon K., Sangmanee P., Plong-on O., Charalsawadi C., Sukasem C., Hnoonual A. Molecular identification of HLA-B75 serotype markers by qPCR: A more inclusive pharmacogenetic approach before carbamazepine prescription. Clinical and Translational Science Vol.17 No.6 (2024). doi:10.1111/cts.13867 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98982
Title
Molecular identification of HLA-B75 serotype markers by qPCR: A more inclusive pharmacogenetic approach before carbamazepine prescription
Corresponding Author(s)
Other Contributor(s)
Abstract
Genetic screening for HLA-B*15:02 before prescribing carbamazepine is standard practice to prevent severe cutaneous adverse reactions in Asian populations. These reactions are associated not only with this allele but also with closely related HLA-B75 serotype markers—HLA-B*15:11 and HLA-B*15:21—which are prevalent in several Asian countries. However, a reliable method for identifying HLA-B75 serotype markers is still not available. We developed an in-house quantitative PCR (qPCR) for HLA-B75 screening and validated it using 303 anonymized DNA samples. Due to inadequate quality control, the qPCR results for 11 samples were excluded. We analyzed the sensitivity and specificity of the test using 93 HLA-typed samples. The concordance between the qPCR method and an established screening method was assessed using 199 HLA-screened samples tested for HLA-B*15:02 at Songklanagarind Hospital, Songkhla, Thailand. All discordant results were confirmed by Sanger sequencing. The qPCR method demonstrated a sensitivity of 100% (95% confidence interval = 83.16%–100.00%) and a specificity of 100% (95% confidence interval = 95.07%–100.00%). Concordance analysis revealed a 96.5% agreement between methods (192/199; 44 positive and 148 negative results). All discordant results were due to HLA-B75 markers not being HLA-B*15:02 (two samples with HLA-B*15:11 and five samples with HLA-B*15:21). In conclusion, this qPCR method could be useful for identifying HLA-B75 carriers at risk of carbamazepine-induced reactions in Asian populations where carriers of HLA-B*15:02, HLA-B*15:11, or HLA-B*15:21 are common.