Significant Association of HLA-B Alleles and Genotypes in Thai Children with Autism Spectrum Disorders: A Case-Control Study.

Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identify HLA-B alleles associated with autism in Thai population, we compared the frequency of HLA-B allele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow-cytometry technology. HLA-B (⁎) 13:02 (P = 0.019, OR = 2.229), HLA-B (⁎) 38:02 (P = 0.049, OR = 1.628), HLA-B (⁎) 44:03 (P = 0.016, OR = 1.645), and HLA-B (⁎) 56:01 (P = 1.78 × 10(-4), OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that the HLA-B (⁎) 18:02 (P = 0.016, OR = 0.375) and HLA-B (⁎) 46:12 (P = 0.008, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, four HLA-B genotypes of autistic patients had statistically significant relationship with control groups, consisting of HLA-B (⁎) 3905/(⁎) 5801 (P = 0.032, OR = 24.697), HLA-B (⁎) 2704/(⁎) 5801 (P = 0.022, OR = 6.872), HLA-B (⁎) 3501/(⁎) 4403 (P = 0.021, OR = 30.269), and HLA-B (⁎) 1801/(⁎) 4402 (P = 0.017, OR = 13.757). This is the first report on HLA-B associated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population.

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

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.