ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO926

Genome-Wide Expression Quantitative Trait Loci Analysis for Circulating miR-1287-5p and miR-339-5p and ESRD in Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Pezzolesi, Marcus G., University of Utah, Salt Lake City, Utah, United States
  • Md Dom, Zaipul I, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
  • O'Neil, Kristina V., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Kobayashi, Hiroki, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
  • Ihara, Katsuhito, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

microRNAs are short endogenous non-coding RNA molecules that are involved in gene regulation and play important roles in the pathogenesis of various kidney diseases. Previously, we identified risk and protective miRNAs (miR-1287-5p and miR-339-5p) strongly associated with progression to end stage renal disease (ESRD) in diabetes. To identify expression quantitative trait loci (eQTL) that influence plasma levels of these miRNAs and onset of ESRD in Type 1 diabetes (T1D), we performed a genome-wide miR-eQTL analysis.

Methods

Plasma levels of the two miRNAs were measured using HTG Molecular Diagnostics’ EdgeSeq platform and genotyping of 325,735 single nucleotide polymorphisms (SNPs) was performed using Illumina’s HumanCoreExome BeadArray in 240 T1D patients. Association analyses between plasma levels of miR-1287-5p and miR-339-5p were used to identify eQTL using linear regression implemented in PLINK. To assess the relationship between the candidate eQTLs and the development of ESRD, we applied logistic regression using an additive model in 437 T1D patients.

Results

Trans miR-eQTL analysis revealed that 13 SNPs that affect plasma levels of miR-1287-5p or miR-339-5p (P<5e-5). Among them, in logistic models, we identified 2 SNPs associated with onset of ESRD: rs4624519 in the LINC02033 (OR: 0.64 (95%CI=0.48-0.85); p=0.0024) and rs10963040 in the CNTLN gene (OR: 1.43 (95%CI= 1.04- 1.96); p=0.028).

Conclusion

We identified SNPs that have regulatory effects on circulating miRNAs and play roles in progression to ESRD in T1D.

Funding

  • NIDDK Support