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*13:01 for dapsone; B*15:02 for carbamazepine and oxcarbazepine; B*58:01, A*33:03 and C*03:02 for allopurinol; C*08:01, C*14:02 and DRB1*12:02 for co-trimoxazole. Whereas, low prevalence of pharmacogenetic markers of SCARs induced by abacavir, B*57:01 and phenytoin, B*56:02/B*56:04 were noticed. The allele frequencies of B*13:01, B*15:02, and B*58:01 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*31:01 and B*57:01 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.
Highlights
Adverse drug reactions are generally classified into two major types, type A and type B
Large variations at both human leukocyte antigen (HLA) class I and class II loci in which 32 alleles for HLA-A, 50 alleles for HLA-B, 33 alleles for HLA-C and 29 alleles for HLA-DRB1 were observed in the study population
Higher frequencies of B∗13:01, B∗15:02, and B∗58:01 alleles which have been proposed as a genetic markers of severe cutaneous adverse reactions (SCARs) induced by dapsone, carbamazepine and allopurinol were observed in this study population compared with those reported in Japanese and Caucasian populations
Summary
Adverse drug reactions are generally classified into two major types, type A and type B. Type A adverse drug reactions are generally related to the mechanism of action and dose of the drugs. Type B adverse drug reactions are unpredictable reactions occurring only in susceptible individuals and generally not related to the mechanism of action of the drugs (Aronson and Ferner, 2005). Phenotypes of cutaneous reactions caused by drugs may range from mild cutaneous reactions such as maculopapular rash, urticaria to life-threatening severe cutaneous adverse reactions (SCARs) such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) (Roujeau, 2005). Identification of factors that are involved in the individual susceptibility to these SCARs may significantly decrease the mortality rate and healthcare costs as well as providing increased safety for drug therapy
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