Progression to type 1 diabetes in the DPT-1 and TN07 clinical trials is critically associated with specific residues in HLA-DQA1-B1 heterodimers
Authors' conclusion
These results unveil the contribution made by DQ to type 1 diabetes progression at individual residues and related protein structures, shedding light on its immunological mechanisms and providing new leads for developing treatment strategies.
Study context
- Population
- Participants in the Diabetes Prevention Trial-Type 1 and the Diabetes Prevention Trial with high-resolution DQA1 and DQB1 genotypes; progression from stages 1 or 2 to stage 3 T1D
- Participants
- 1,216 participants
- Outcome
- Association of HLA-DQ AAs and structures with time-to-onset of T1D (progression from stages 1 or 2 to stage 3)
Methodological detailshierarchically organised haplotype association analysis (HOH), Cox regression
- Hierarchically organised haplotype association analysis (HOH)
- Cox regression
Main finding
As reported in the abstract
Heterodimerisation increased genetic diversity from empirically observed haplotypes to possible heterodimers
43 to 186
Amino acids (AAs) on the α-chain contributing to association of DQ with progression (−16α, −13α, −6α, α22, α23, α44, α72, α157)
8
AAs on the β-chain contributing to association of DQ with progression (−18β, β9, β13, β26, β57, β135)
6
Original publication
Progression to type 1 diabetes in the DPT-1 and TN07 clinical trials is critically associated with specific residues in HLA-DQA1-B1 heterodimers. Diabetologia. Published 1 October 2024. doi:10.
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