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

P. Tran, Fran Dong, Khaled Bin Satter, Katherine P. Richardson, Roshni Patel, L. K. Tran, D. Hopkins, R. Kolhe, Kathleen C. Waugh, M. Rewers, S. 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。
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