Endocrines (Sep 2022)

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

  • 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

DOI
https://doi.org/10.3390/endocrines3030048
Journal volume & issue
Vol. 3, no. 3
pp. 570 – 577

Abstract

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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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