AUTHOR=Puangpetch Apichaya , Koomdee Napatrupron , Chamnanphol Montri , Jantararoungtong Thawinee , Santon Siwalee , Prommas Santirhat , Hongkaew Yaowaluck , Sukasem Chonlaphat 

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

JOURNAL=Frontiers in Genetics

VOLUME=5

YEAR=2015

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2014.00478

DOI=10.3389/fgene.2014.00478

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> There are 3 classes of <italic>HLA</italic> molecules; <italic>HLA</italic> class I, II and III, of which different classes have different functions. <italic>HLA-B</italic> gene which belongs to <italic>HLA</italic> class I play an important role predicting drug hypersensitivity.</p><p><bold>Materials and Methods:</bold> Nine hundred and eighty-six Thai subjects who registered at a pharmacogenomics laboratory were determined for <italic>HLA-B</italic> genotype using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP).</p><p><bold>Results:</bold> In this study, <italic>HLA-B</italic> alleles did not deviate from Hardy-Weinberg equilibrium (<italic>P</italic> &gt; 0.05). The most common <italic>HLA-B</italic> alleles observed in this population were <italic>HLA-B</italic><sup>*</sup><italic>46:01</italic> (11.51%), <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> (8.62%), <italic>HLA-B</italic><sup>*</sup><italic>40:01</italic> (8.22%), <italic>HLA-B</italic><sup>*</sup><italic>15:02</italic> (8.16%) and <italic>HLA-B</italic><sup>*</sup><italic>13:01</italic> (6.95%). This finding revealed that <italic>HLA-B</italic> allele frequency in the Thai population was consistent with the Chinese population (<italic>p</italic> &gt; 0.05), however, differed from the Malaysian population (<italic>p</italic> &lt; 0.05). The top five <italic>HLA-B</italic> genotypes were <italic>HLA-B</italic><sup>*</sup><italic>40:01/46:01</italic> (2.13%), <italic>HLA-B</italic><sup>*</sup><italic>46:01/46:01</italic> (2.03%), <italic>HLA-B</italic><sup>*</sup><italic>40:01/58:01</italic> (2.03%), <italic>HLA-B</italic><sup>*</sup><italic>46:01/58:01</italic> (1.93%) and <italic>HLA-B</italic><sup>*</sup><italic>15:02/46:01</italic> (1.83%). This study found that 15.92% of Thai subjects carry <italic>HLA-B</italic><sup>*</sup><italic>15:02</italic>, which has been associated with carbamazepine-induced severe cutaneous adverse drug reactions (SCARs). Moreover, 16.33% of Thai subjects carry the <italic>HLA-B</italic><sup>*</sup><italic>58:01</italic> allele, which has been associated with allopurinol-induced SCARs.</p><p><bold>Conclusion:</bold> This study demonstrates a high diversity of <italic>HLA-B</italic> polymorphisms in this Thai population. The high frequency of <italic>HLA-B</italic> pharmacogenomic markers in the population emphasizes the importance of such screening to predict/avoid drug hypersensitivity.</p>