AUTHOR=Nakkam Nontaya , Konyoung Parinya , Kanjanawart Sirimas , Saksit Niwat , Kongpan Thachanan , Khaeso Kanyarat , Khunarkornsiri Usanee , Dornsena Areerat , Tassaneeyakul Wongwiwat , Tassaneeyakul Wichittra 

TITLE=HLA Pharmacogenetic Markers of Drug Hypersensitivity in a Thai Population

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00277

DOI=10.3389/fgene.2018.00277

ISSN=1664-8021

ABSTRACT=<p>Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) are potentially life-threatening cutaneous reactions caused by several drugs. Recently, a number of genes encoding for human antigen presenting proteins, <italic>HLA</italic> alleles, have been discovered as valid pharmacogenetic markers for prediction of these life-threatening reactions. This study was aimed to determine the distribution of <italic>HLA</italic> alleles including the <italic>HLA</italic> class I and class II genes in 183 unrelated individuals of a Thai population using high resolution <italic>HLA</italic> genotyping in order to obtain 2-field data (4-digit resolution) and compare the frequencies of the <italic>HLA</italic> alleles that have been proposed as markers of SCARs with other ethnics. Results revealed a high prevalence of pharmacogenetic markers of drug-induced SCARs e.g., <italic>B</italic><sup>*</sup><italic>13:01</italic> for dapsone<italic>; B</italic><sup>*</sup><italic>15:02</italic> for carbamazepine and oxcarbazepine; <italic>B</italic><sup>*</sup><italic>58:01, A</italic><sup>*</sup><italic>33:03</italic> and <italic>C</italic><sup>*</sup><italic>03:02</italic> for allopurinol; <italic>C</italic><sup>*</sup><italic>08:01, C</italic><sup>*</sup><italic>14:02</italic> and <italic>DRB1</italic><sup>*</sup><italic>12:02</italic> for co-trimoxazole. Whereas, low prevalence of pharmacogenetic markers of SCARs induced by abacavir, <italic>B</italic><sup>*</sup><italic>57:01</italic> and phenytoin, <italic>B</italic><sup>*</sup><italic>56:02/B</italic><sup>*</sup><italic>56:04</italic> were noticed. The allele frequencies of <italic>B</italic><sup>*</sup><italic>13:01, B</italic><sup>*</sup><italic>15:02</italic>, and <italic>B</italic><sup>*</sup><italic>58:01</italic> observed in a Thai population were significantly higher than those reported in Japanese and Caucasian populations. Similar to those observed in other Southeast Asian populations, low frequencies of <italic>A</italic><sup>*</sup><italic>31:01</italic> and <italic>B</italic><sup>*</sup><italic>57:01</italic> alleles were noted in the study population. Based on the frequencies of <italic>HLA</italic> pharmacogenetic markers, Thai and other Southeast Asian populations may at higher risk of drug-induced SCARs compared with Caucasian population.</p>