HLA-B allele and haplotype diversity among Thai patients identified by PCR-SSOP: evidence for high risk of drug-induced hypersensitivity

Abstract

Background: There are 3 classes of HLA molecules; HLA class I, II and III, of which different classes have different functions. HLA-B gene which belongs to HLA class I play an important role predicting drug hypersensitivity.Materials and Methods: Nine hundred and eighty-six Thai subjects who registered at a pharmacogenomics laboratory were determined for HLA-B genotype using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP).Results: In this study, HLA-B alleles did not deviate from Hardy-Weinberg equilibrium (P > 0.05). The most common HLA-B alleles observed in this population were HLA-B*46:01 (11.51%), HLA-B*58:01 (8.62%), HLA-B*40:01 (8.22%), HLA-B*15:02 (8.16%) and HLA-B*13:01 (6.95%). This finding revealed that HLA-B allele frequency in the Thai population was consistent with the Chinese population (p > 0.05), however, differed from the Malaysian population (p < 0.05). The top five HLA-B genotypes were HLA-B*40:01/46:01 (2.13%), HLA-B*46:01/46:01 (2.03%), HLA-B*40:01/58:01 (2.03%), HLA-B*46:01/58:01 (1.93%) and HLA-B*15:02/46:01 (1.83%). This study found that 15.92% of Thai subjects carry HLA-B*15:02, which has been associated with carbamazepine-induced severe cutaneous adverse drug reactions (SCARs). Moreover, 16.33% of Thai subjects carry the HLA-B*58:01 allele, which has been associated with allopurinol-induced SCARs.Conclusion: This study demonstrates a high diversity of HLA-B polymorphisms in this Thai population. The high frequency of HLA-B pharmacogenomic markers in the population emphasizes the importance of such screening to predict/avoid drug hypersensitivity.

Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population

“…Moreover, there was no significant association between the HLA-B*15:02 with phenytoin-related SCAR irrespective of cutaneous adverse reaction phenotypes ( Table 2). In addition, the frequency of the HLA-B*15:02 in the phenytoin-tolerant controls (14.13%) in this study was comparable with those previously reported in the general Thai population (16.33-16.75%) [26,27]. Consistent with those observed when compared with the phenytoin-tolerant controls, there also was no significant association between the HLA-B*15:02 with phenytoin-related SJS/TEN compared with the general Thai population (Table 3).…”

“…It is necessary to point out here that the PCR-sequencespecific oligonucleotide probes technique that was used for HLA genotyping in the present study as well as in the previous study was reported by Puangpetch et al [27]. Ambiguous results for HLA-B*56:02 or HLA-B*56:04 genotypes may occur when using this HLA genotyping technique.…”

“…Compared with the data reported previously in a general Thai population [26,27] (Table 3). For the phenytoinrelated DRESS, compared with the general Thai population, only the HLA-B*56:02 allele showed a statistically significant difference (OR = 49.25, 95% CI = 2.97-815.54, P = 0.0413) ( Table 3).…”

“…b Data obtained from a report by Puangpetch et al [27], in which the total number of participants was 986.…”

HLA Class I Alleles Associated with Mortality in Thai Military Recruits with HIV-1 CRF01_AE Infection

“…For the alleles with significant associations-and for other alleles in this study-there is a low frequency of polymorphisms within the Thai population: for example, HLA B*51 is predominantly HLA B*51:01 and HLA B*46 is commonly HLA B*46:01. 24 The latter is part of a common Thai haplotype consisting of A*02:07-Cw*01-B*46:01-DRB1*09-DQB1*03:03. It is, therefore, unlikely that higher resolution typing to detect these infrequent polymorphisms with the sample size in this study would significantly confound these results, but additional studies with highresolution typing should be pursued.…”