Dual approaches in pharmacogenetics: Developing PCR-SSP and RT-PCR methods for HLA-B*13:01 screening to prevent dapsone and Co-trimoxazole SCARs

Autor: Jirapat Attapong, Chollanot Kaset, Nontaya Nakkam, Wichittra Tassaneeyakul, Nuanjun Wichukchinda, Sirinart Chomean
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 15, Pp e34977- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2024.e34977
Popis: Dapsone and co-trimoxazole are potent antibiotics for treating various infections and inflammations. However, several studies reported the strongly association between severe cutaneous adverse drug reactions (SCARs) to both drugs and the HLA-B*13:01 allele. Rapid and reliable screening for the HLA-B*13:01 allele can mitigate the risk of dapsone-induced SCARs. We developed two methods, multiplex sequence-specific primer PCR (PCR-SSP) and real-time PCR (RT-PCR), tailored for different clinical settings. These methods were optimized to minimize false positives among the Thai population. Clinical validation demonstrated excellent reproducibility, with both methods showing 100 % concordance in repeated tests. PCR-SSP achieved a limit of detection as low as 100 pg of genomic DNA, while RT-PCR reached 1 pg. Overall statistical accuracy was 100.00 % (95 % CI: 98.18 %–100.00 %). Screening for drug-related HLA alleles is crucial for reducing mortality from severe cutaneous adverse drug reactions, especially dapsone hypersensitivity syndrome (DHS) and dapsone-induced hypersensitivity reactions (DIHRs). Our screening approach for dapsone can also be extended to co-trimoxazole, representing a significant advancement in personalized medicine and preemptive pharmacogenetic testing for tailored patient care and safety, albeit further validation in diverse ethnic populations is warranted to ensure universal applicability.
Databáze: Directory of Open Access Journals