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HLA-B allele and haplotype diversity among Thai patients identified by PCR-SSOP: evidence for high risk of drug-induced hypersensitivity

Background: There are 3 classes of HLA molecules; HLA class I, II and III, of which different classes have different functions. HLA-B gene which belongs to HLA class I play an important role predicting drug hypersensitivity. Materials and Methods: Nine hundred and eighty-six Thai subjects who regist...

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Detalles Bibliográficos
Autores principales: Puangpetch, Apichaya, Koomdee, Napatrupron, Chamnanphol, Montri, Jantararoungtong, Thawinee, Santon, Siwalee, Prommas, Santirhat, Hongkaew, Yaowaluck, Sukasem, Chonlaphat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302987/
https://www.ncbi.nlm.nih.gov/pubmed/25657656
http://dx.doi.org/10.3389/fgene.2014.00478
Descripción
Sumario:Background: There are 3 classes of HLA molecules; HLA class I, II and III, of which different classes have different functions. HLA-B gene which belongs to HLA class I play an important role predicting drug hypersensitivity. Materials and Methods: Nine hundred and eighty-six Thai subjects who registered at a pharmacogenomics laboratory were determined for HLA-B genotype using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP). Results: In this study, HLA-B alleles did not deviate from Hardy-Weinberg equilibrium (P > 0.05). The most common HLA-B alleles observed in this population were HLA-B(*)46:01 (11.51%), HLA-B(*)58:01 (8.62%), HLA-B(*)40:01 (8.22%), HLA-B(*)15:02 (8.16%) and HLA-B(*)13:01 (6.95%). This finding revealed that HLA-B allele frequency in the Thai population was consistent with the Chinese population (p > 0.05), however, differed from the Malaysian population (p < 0.05). The top five HLA-B genotypes were HLA-B(*)40:01/46:01 (2.13%), HLA-B(*)46:01/46:01 (2.03%), HLA-B(*)40:01/58:01 (2.03%), HLA-B(*)46:01/58:01 (1.93%) and HLA-B(*)15:02/46:01 (1.83%). This study found that 15.92% of Thai subjects carry HLA-B(*)15:02, which has been associated with carbamazepine-induced severe cutaneous adverse drug reactions (SCARs). Moreover, 16.33% of Thai subjects carry the HLA-B(*)58:01 allele, which has been associated with allopurinol-induced SCARs. Conclusion: This study demonstrates a high diversity of HLA-B polymorphisms in this Thai population. The high frequency of HLA-B pharmacogenomic markers in the population emphasizes the importance of such screening to predict/avoid drug hypersensitivity.