Association of HLA-DQ Heterodimer Residues -18β and β57 With Progression From Islet Autoimmunity to Diabetes in the Diabetes Prevention Trial-Type 1.

ABSTRACT:

Objective

The purpose was to test the hypothesis that the HLA-DQαβ heterodimer structure is related to the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).

Research design and methods

Next-generation targeted sequencing was used to genotype HLA-DQA1-B1 class II genes in 670 subjects in the Diabetes Prevention Trial-Type 1 (DPT-1). Coding sequences were translated into DQ α- and β-chain amino acid residues and used in hierarchically organized haplotype (HOH) association analysis to identify motifs associated with diabetes onset.

Results

The opposite diabetes risks were confirmed for HLA DQA1*03:01-B1*03:02 (hazard ratio [HR] 1.36; P = 2.01 ∗ 10-3) and DQA1*03:03-B1*03:01 (HR 0.62; P = 0.037). The HOH analysis uncovered residue -

SUBMITTER: Zhao LP 

PROVIDER: S-EPMC9274226 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature