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, HLA alleles, have been discovered as valid pharmacogenetic markers for prediction of these life-threatening reactions. This study was aimed to determine the distribution of HLA alleles including the HLA class I and class II genes in 183 unrelated individuals of a Thai population using high resolution HLA genotyping in order to obtain 2-field data (4-digit resolution) and compare the frequencies of the HLA 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., B*1301 for dapsone; B*1502 for carbamazepine and oxcarbazepine; B*5801, A*3303 and C*0302 for allopurinol; C*0801, C*1402 and DRB1*1202 for co-trimoxazole. Whereas, low prevalence of pharmacogenetic markers of SCARs induced by abacavir, B*5701 and phenytoin, B*5602/B*5604 were noticed. The allele frequencies of B*1301, B*1502, and B*5801 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 A*3101 and B*5701 alleles were noted in the study population. Based on the frequencies of HLA pharmacogenetic markers, Thai and other Southeast Asian populations may at higher risk of drug-induced SCARs compared with Caucasian population.