Abstract
Human leukocyte antigen (HLA) class I and II are known to have association with severe cutaneous adverse reactions (SCARs) when exposing to certain drug treatment. Due to genetic differences at population level, drug hypersensitivity reactions are varied, and thus common pharmacogenetics markers for one country might be different from another country, for instance, HLA-A*31:01 is associated with carbamazepine (CBZ)-induced SCARs in European and Japanese while HLA-B*15:02 is associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among Taiwanese and Southeast Asian. Such differences pose a major challenge to prevent drug hypersensitivity when pharmacogenetics cannot be ubiquitously and efficiently translated into clinic. Therefore, a population-wide study of the distribution of HLA-pharmacogenetics markers is needed. This work presents a study of Thai HLA alleles on both HLA class I and II genes from 470 unrelated Thai individuals by means of polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) in which oligonucleotide probes along the stretches of HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 genes were genotyped. These 470 individuals were selected according to their regional locations, which were from North, Northeast, South, Central, and a capital city, Bangkok. Top ranked HLA alleles in Thai population include HLA-A*11:01 (26.06%), -B*46:01 (14.04%), -C* 01:02 (17.13%), -DRB1*12:02 (15.32%), -DQA1*01:01 (24.89%), and -DQB1*05:02 (21.28%). The results revealed that the distribution of HLA-pharmacogenetics alleles from the South had more HLA-B75 family that a typical HLA-B*15:02 pharmacogenetics test for SJS/TEN screening would not cover. Besides the view across the nation, when compared HLA alleles from Thai population with HLA alleles from both European and Asian countries, the distribution landscape of HLA-associated drug hypersensitivity across many countries could be observed. Consequently, this pharmacogenetics database offers a comprehensive view of pharmacogenetics marker distribution in Thailand that could be used as a reference for other Southeast Asian countries to validate the feasibility of their future pharmacogenetics deployment.
Highlights
Human leukocyte antigen (HLA) gene is located on chromosome 6p21, which was considered the most polymorphic of human genetic system (Shiina et al, 2009)
We found that the alleles HLA-A*11:01, -A*24:02, -A*02:03, -A*33:03, -A*02:07, and -A*02:01 were more common than the others
We examined the frequency distribution of HLA class I and II alleles in five regions of Thailand by HLA-typing of 470 healthy individuals using polymerase chain reaction (PCR)-SSOs probe
Summary
Human leukocyte antigen (HLA) gene is located on chromosome 6p21, which was considered the most polymorphic of human genetic system (Shiina et al, 2009). HLA encodes cell surface molecules that present antigenic peptides to the T-cell receptor (TCR) on T cells (Sette and Sidney, 1998). There are two main classes of HLA allele. HLA class I and II encode cell surface heterodimers that play a role in antigen presentation, tolerance, and self/nonself-recognition. HLA class I molecules gather peptides that have been synthesized within the individual nucleated cell, three main HLA class I genes including HLA-A, HLA-B, and HLA-C (Howell et al, 2010). Whereas HLA class II molecules gather exogenously synthesized peptide ligands by endocytic pathway and expressed with antigen-presenting cells (APCs), six main HLA class II genes including HLA-DPA1, HLADPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1 (Ulvestad et al, 1994). There have been reported associations between various HLA alleles and different adverse drug reactions, especially severe cutaneous adverse reactions (SCARs)
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