DNA typing of HLA-A, -C, -B, AND -DRB1 in the children with autism in the Republic of Macedonia

Abstract

In the present study, we report the fi rst DNA analysis of HLA class I and class II alleles in Macedonian autistic subjects. We have analyzed the HLA-A, -C, -B, DRB1 genotypes of 35 autistic patients, and 98 healthy unrelated Macedonians (control group). HLA DNA typing of class I genes was performed using a Reverse Line Strip method (RLS), and the Sequencing Based Typing method (SBT) was used for typing of class II genes. In the autistic subjects for HLA-A locus 14 alleles have been identifi ed with 2 being predominant *02 (25.7 %), and *24 (18.6 %). Among the 11 identifi ed HLA-C alleles, 3 were predominant such as *12 (20.0 %), *07 (17.1%), and *03 (12.9 %). Among the 18 identifi ed HLA-B alleles, 2 were predominant: *51 (18.6 %), and *18 (11.4%). For HLA-DRB1 locus, 10 alleles have been identifi ed with 2 of them predominant such as: *11 (21.4 %), and *01 (14.3 %). The allele and haplotype frequencies in the patients group were compared to those of 98 control subjects. Our results showed signifi cantly increased frequencies of HLA-C*03 (OR = 2.74*; χ2 = 4.68; p = 0.03), and HLA-DRB1*01 (OR = 3.10*; χ2 = 6.26; p = 0.012) alleles in autistic patients when compared to the controls. The most frequent haplotype frequencies in autistic sample were A*11-C*12-B*52-DRB1*15 (2.9%), A*24-C*03-B*55-DRB1*16 (2.9 %), and A*24-C*03-B*55-DRB1*16 (2.9 %), but they were not statistically signifi cant when compared to the control group. None of our patients carried allele or haplotype, which were protective in our population. Hardy-Weinberg equilibrium in autistic group showed that HLA-A (p < 0.03), HLAC (p < 0.04), and HLA-DRB1 (p < 0.002) loci were in linkage disequilibria. In the control group, we found only for the HLA-DRB1 locus linkage disequilibrium (p < 0.002). Our results demonstrated the association of HLAC*03 and HLA-DRB1*01 alleles with Macedonian autistic patients.