单基因自身免疫性糖尿病的表型表现与 1 型糖尿病遗传风险有关。

Diabetes Pub Date : 2025-02-01 DOI:10.2337/db24-0485

Amber M Luckett, Gareth Hawkes, Harry D Green, Elisa De Franco, William A Hagopian, Bart O Roep, Michael N Weedon, Richard A Oram, Matthew B Johnson

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引用次数: 0

摘要

免疫平衡关键基因中的致病变异可导致单基因自身免疫性糖尿病。一些携带致病变异基因的人即使患上其他自身免疫性疾病，也不会发展成自身免疫性糖尿病。我们旨在确定 1 型糖尿病多基因风险是否会导致单基因自身免疫性糖尿病的表型表现。我们使用 67 个 SNP 1 型糖尿病遗传风险评分（T1D-GRS）来确定 62 名单基因自身免疫性糖尿病患者和 180 名非自身免疫性新生儿糖尿病（NDM）对照者的多基因风险。我们使用人群对照组（10405 人）和 1 型糖尿病患者（285 人）作为比较组。与非自身免疫性 NDM（平均 11.3 vs. 9.8；P=1.7×10-5）和对照组（平均 10.3；P=7.5×10-6）相比，单基因自身免疫性糖尿病患者的 T1D-GRS 较高，但明显低于 1 型糖尿病患者（14.9；P=3.3×10-21）。这些差异的原因是单基因自身免疫性糖尿病病例具有较高的 II 类 HLA 遗传风险，特别是来自 DRB1*03:01-DQA1*05:01-DQB1*02:01 单倍型 (DR3-DQ2) 的遗传风险。

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Type 1 Diabetes Genetic Risk Contributes to Phenotypic Presentation in Monogenic Autoimmune Diabetes.

Article highlights: There is variability in early-onset autoimmune diabetes presentation in individuals with monogenic autoimmunity; the mechanism(s) underlying this is unclear. We examined whether type 1 diabetes (T1D) polygenic risk contributes to clinical phenotype in monogenic autoimmune diabetes. Individuals with monogenic autoimmune diabetes had higher T1D genetic risk scores compared with control cohorts, driven largely by increased presence of T1D-risk DR3-DQ2 haplotype. Established T1D polygenic risk alleles, particularly class II HLA genes, contribute to clinical presentation in monogenic autoimmunity.

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Diabetes

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