Determination of T1D-Susceptible HLA DR-DQ Haplotypes in Yakuts Using Three Single Nucleotide Polymorphisms

Abstract

The purpose of this study was to determine T1D-susceptible HLA DR-DQ haplotypes in Yakuts using 3 single nucleotide polymorphisms (rs3104413C/G, rs2854275G/T and rs9273363A/C). A total of 92 patients with a verified diagnosis of T1D (Group 1) were examined. The comparison group consisted of 210 people (Group 2) without autoimmune diseases and without hereditary predisposition. All participants were Yakuts by ethnicity. According to the results of genotyping, it was established that the haplotype DRB1*03:01-DQA1*05:01-DQB1*02:01 corresponds to the rs3104413C/C-rs2854275T/T combination and the rs3104413C/G-rs2854275G/T-rs9273363C/C combination. DRB1*04:01–DQA1*03:01-DQB1*03:02 haplotype (DR4-DQ8) is the rs3104413G/G-rs9273363A/C combination, the rs3104413C/G-rs2854275G/G-rs9273363A/C combination, and the rs3104413C/G-rs2854275G/G-rs9273363A/A combination. DR3/4-DQ8 haplotype is the rs3104413C/G-rs2854275G/T-rs9273363A/A combination and the rs3104413C/G-rs2854275G/T-rs9273363A/C combination. DRB1*04:01-DQA1*03:01-DQB1*03:01 haplotype is the rs3104413G/G-rs9273363C/C combination, the rs3104413C/G-rs2854275G/G-rs9273363C/C combination, and the rs3104413C/G-rs2854275G/T-rs9273363C/C combination. A combination of rs3104413C/C with rs2854275G/G was characterized by the absence of DR3 and DR4, which may be due to the presence of a different genetic variant in these individuals. A combination of rs3104413C/C with rs2854275G/T was characterized by the presence of only one type of DR3 and a variant of the type that does not belong to either DR3 or DR4. An analysis of the evaluation of the effectiveness of a diagnostic test using the Youden index demonstrated significance for all combinations of genotypes of the studied polymorphisms.

Keywords

• haplotype
• single nucleotide polymorphism
• Yakuts
• type 1 diabetes