Serum IL-1ra Is Associated with but Has No Genetic Link to Type 1 Diabetes.

Endocrines Pub Date : 2022-09-01 Epub Date: 2022-09-13 DOI:10.3390/endocrines3030048

Paul M H Tran, Fran Dong, Khaled Bin Satter, Katherine P Richardson, Roshni Patel, Lynn K H Tran, Diane Hopkins, Ravindra Kolhe, Kathleen Waugh, Marian Rewers, Sharad Purohit

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Abstract

Interleukin-1 antagonism is a proposed biomarker and potential therapy for the delay and/or treatment of type 1 diabetes (T1D). We evaluated the role of circulating interleukin-1 receptor antagonist (IL-1ra) in a prospectively monitored cohort of T1D patients. In order to determine a mechanistic association between IL-1ra and T1D, we performed co-localization analyses between serum IL-1ra protein quantitative trait loci and T1D genome-wide analysis studies. Adjusting for human leukocyte antigen (HLA) genotypes, first degree relative status, gender, and age, serum levels of IL-1ra were lower in subjects who progressed to T1D compared to the controls (p = 0.023). Our results suggest that females have higher levels of IL-1ra compared to males (p = 0.005). The 2q14.1 region associated with serum IL-1ra levels is not associated with a risk of developing T1D. Our data suggest that IL-1 antagonism by IL-1ra is not an effective therapy in T1D, but IL-1ra may be a biomarker for progression to T1D.

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血清IL-1ra与1型糖尿病相关，但无遗传联系

白细胞介素-1拮抗作用是一种拟议的生物标志物，也是延迟和/或治疗1型糖尿病（T1D）的潜在疗法。我们评估了循环白细胞介素-1受体拮抗剂（IL-1ra）在前瞻性监测的T1D患者队列中的作用。为了确定IL-1ra和T1D之间的机制联系，我们在血清IL-1ra蛋白定量性状基因座和T1D全基因组分析研究之间进行了共定位分析。调整人类白细胞抗原（HLA）基因型、一级相对状态、性别和年龄，与对照组相比，进展为T1D的受试者的血清IL-1ra水平较低（p=0.023）。我们的研究结果表明，女性的IL-1ra水平高于男性（p=0.005）。与血清IL-1ra浓度相关的2q14.1区域与T1D的风险无关。我们的数据表明，IL-1ra对IL-1的拮抗作用不是治疗T1D的有效方法，但IL-1ra可能是进展为T1D的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Endocrines

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11 weeks