ArticleDiabetologia2021
HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes.
Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Association between type 1 diabetes mellitus and dental caries in children and adolescents: a meta-analysis and Mendelian randomization study.Frontiers in endocrinology · 2026Pooled it
- Harnessing Machine Learning, a Subset of Artificial Intelligence, for Early Detection and Diagnosis of Type 1 Diabetes: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Structural Modulation and Binding of HLA-DQ8 by Cysteine-to-Serine Mutated Insulin Peptide: Insights from Molecular Dynamics Simulations.International journal of molecular sciences · 2026Article
- Immunogenetics and TCR expression patterns together predict future T1D onset from multi-omic datasets.Frontiers in genetics · 2026Article
- HLA genotyping and clinical characteristics of early-onset and late-onset anti-LGI1 encephalitis: a single-center cohort study in China.Frontiers in immunology · 2026Article
- Evaluation of distinct and similar pathological features between diabetes and Alzheimer's disease.EXCLI journal · 2026Review
- [Research progress and optimization strategies for early screening of type 1 diabetes].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Review
- The epidemiology of type 1 diabetes mellitus in older adults.Nature reviews. Endocrinology · 2025Review
- HLA-CPediatric diabetes · 2025Article
- Does HLA explain the high incidence of childhood-onset type 1 diabetes in the Canary Islands? The role of Asp57 DQB1 molecules.BMC pediatrics · 2024Article
- Fifty years of HLA-associated type 1 diabetes risk: history, current knowledge, and future directions.Frontiers in immunology · 2024Review
- Next-generation sequencing reveals additional HLA class I and class II alleles associated with type 1 diabetes and age at onset.Frontiers in immunology · 2024Article
- Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets.American journal of human genetics · 2023Article
- Review
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes.
methodsA total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing.
resultsThe susceptible DR3 (β = -0.09, p = 0.0009) and DR4-DQ8 (β = -0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = -0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. CONCLUSIONS/
interpretationIn addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies.
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