Monocyte miRNAs Are Associated With Type 2 Diabetes

Diabetes. 2022 Apr 1;71(4):853-861. doi: 10.2337/db21-0704.

Abstract

miRNAs are small noncoding RNAs that may contribute to common diseases through epigenetic regulation of gene expression. Little is known regarding the role of miRNAs in type 2 diabetes (T2D). We performed miRNA sequencing and transcriptomic profiling of peripheral monocytes from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA) (N = 1,154). We examined associations between miRNAs and prevalent impaired fasting glucose and T2D and evaluated the T2D-associated miRNA effect on incident T2D. Of 774 detected miRNAs, 6 (miR-22-3p, miR-33a-5p, miR-181c-5p, miR-92b-3p, miR-222-3p, and miR-944) were associated with prevalent T2D. For five of the six miRNAs (all but miR-222-3p), our findings suggest a dose-response relationship with impaired fasting glucose and T2D. Two of the six miRNAs were associated with incident T2D (miR-92b-3p: hazard ratio [HR] 1.64, P = 1.30E-03; miR-222-3p: HR 1.97, P = 9.10E-03) in the highest versus lowest tertile of expression. Most of the T2D-associated miRNAs were also associated with HDL cholesterol concentrations. The genes targeted by these miRNAs belong to key nodes of a cholesterol metabolism transcriptomic network. Higher levels of miRNA expression expected to increase intracellular cholesterol accumulation in monocytes are linked to an increase in T2D risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Diabetes Mellitus, Type 2* / genetics
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Glucose
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Monocytes / metabolism

Substances

  • MIRN944 microRNA, human
  • MicroRNAs
  • Glucose