HLA Pharmacogenetic Markers of Drug Hypersensitivity in a Thai Population

Abstract

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, <i>HLA</i> alleles, have been discovered as valid pharmacogenetic markers for prediction of these life-threatening reactions. This study was aimed to determine the distribution of <i>HLA</i> alleles including the <i>HLA</i> class I and class II genes in 183 unrelated individuals of a Thai population using high resolution <i>HLA</i> genotyping in order to obtain 2-field data (4-digit resolution) and compare the frequencies of the <i>HLA</i> 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., <i>B</i>^*<i>13:01</i> for dapsone<i>; B</i>^*<i>15:02</i> for carbamazepine and oxcarbazepine; <i>B</i>^*<i>58:01, A</i>^*<i>33:03</i> and <i>C</i>^*<i>03:02</i> for allopurinol; <i>C</i>^*<i>08:01, C</i>^*<i>14:02</i> and <i>DRB1</i>^*<i>12:02</i> for co-trimoxazole. Whereas, low prevalence of pharmacogenetic markers of SCARs induced by abacavir, <i>B</i>^*<i>57:01</i> and phenytoin, <i>B</i>^*<i>56:02/B</i>^*<i>56:04</i> were noticed. The allele frequencies of <i>B</i>^*<i>13:01, B</i>^*<i>15:02</i>, and <i>B</i>^*<i>58:01</i> 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 <i>A</i>^*<i>31:01</i> and <i>B</i>^*<i>57:01</i> alleles were noted in the study population. Based on the frequencies of <i>HLA</i> pharmacogenetic markers, Thai and other Southeast Asian populations may at higher risk of drug-induced SCARs compared with Caucasian population.