黑死病保护基因突变在1型糖尿病及其并发症和常见病毒感染中的作用尚不明确

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-05-29 DOI:10.1016/j.diabres.2025.112287

Bartosz Słomiński , Julia Gładysz , Maria Skrzypkowska , Monika Ryba-Stanisławowska , Dariusz Nowicki , Agnieszka Szalewska-Pałasz , Małgorzata Myśliwiec

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引用次数: 0

摘要

由于ERAP2与感染和自身免疫性疾病有关，我们假设rs9939609 ERAP2多态性（在黑死病前后的人类样本中观察到的等位基因频率）可能影响1型糖尿病（T1D）、其并发症和常见的病毒感染。方法400例T1D患者和300例年龄匹配的健康对照。分析了ERAP2多态性与T1D并发症和合并症、儿童常见病毒感染史以及T1D患者炎症状态的关系。结果T等位基因与糖尿病发病风险降低有关，以不同的方式调节其并发症，并对T1D患者的炎症状态有不同的影响。我们的研究结果还表明，不同ERAP2变体在单核细胞亚群的相关性、CD4 + cd25高FOXP3+调节性T细胞的定量状态以及对常见儿童病毒感染的易感性方面存在统计学差异。结论rs2549794 ERAP2多态性可能是T1D并发症和合并症易感性的遗传标记，进一步强调了ERAP2介导通路在T1D并发症和合并症发病中的作用。这些结果也提供了新的证据，支持自身免疫性疾病和传染性疾病驱动的基因座平衡选择的假设。

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Black Death protective gene mutation shows ambiguous role in type 1 diabetes, its complications, and common viral infections

Aims

Because ERAP2 is implicated in infections and autoimmune diseases, we hypothesize that the rs9939609 ERAP2 polymorphism, with allele frequencies observed in human samples from both before and after the Black Death, may influence type 1 diabetes (T1D), its complications, and common viral infections.

Methods

We examined 400 patients with T1D and 300 healthy, age-matched controls. The analysis focused on the ERAP2 polymorphism in relation to T1D complications and comorbidities, the history of common childhood viral infections, and the inflammatory status of T1D patients.

Results

The T allele is linked to a decreased risk of developing diabetes, modulates its complications in a differential manner, and has diverse effects on the inflammatory status of T1D patients. Our results also indicate statistically significant differences in the correlation of monocyte subsets, the quantitative status of CD4 + CD25^high FOXP3⁺ regulatory T cells, and susceptibility to common childhood viral infections between different ERAP2 variants.

Conclusions

Our findings suggest that the rs2549794 ERAP2 polymorphism may serve as a genetic marker for susceptibility to T1D complications and comorbidities, further emphasizing the role of ERAP2-mediated pathways in their etiology. These results also provide new evidence supporting the hypothesis of balancing selection at this locus, driven by autoimmune and infectious diseases.

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.