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 x 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.