Journal of Translational Medicine (Nov 2021)

MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS

  • Federica Barutta,
  • Beatrice Corbetta,
  • Stefania Bellini,
  • Simonetta Guarrera,
  • Giuseppe Matullo,
  • Michela Scandella,
  • Casper Schalkwijk,
  • Coen D. Stehouwer,
  • Nish Chaturvedi,
  • Sabita S. Soedamah-Muthu,
  • Marilena Durazzo,
  • Gabriella Gruden

DOI
https://doi.org/10.1186/s12967-021-03142-4
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 10

Abstract

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Abstract Background MicroRNA-146a-5p (miR-146a-5p) is a key regulator of inflammatory processes. Expression of miR-146a-5p is altered in target organs of diabetic complications and deficiency of miR-146a-5p has been implicated in their pathogenesis. We investigated if serum miR-146a-5p levels were independently associated with micro/macrovascular complications of type 1 diabetes (DM1). Methods A nested case–control study from the EURODIAB PCS of 447 DM1 patients was performed. Cases (n = 294) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. Total RNA was isolated from all subjects and miR-146a-5p levels measured by qPCR. Both the endogenous controls U6 snRNA and the spike (Cel-miR-39) were used to normalize the results. Logistic regression analysis was carried out to investigate the association of miR-146a-5p with diabetes complications. Results MiR-146a-5p levels were significantly lower in cases [1.15 (0.32–3.34)] compared to controls [1.74 (0.44–6.74) P = 0.039]. Logistic regression analysis showed that levels of miR-146a-5p in the upper quartile were inversely associated with reduced odds ratio (OR) of all complications (OR 0.34 [95% CI 0.14–0.76]) and particularly with cardiovascular diseases (CVD) (OR 0.31 [95% CI 0.11–0.84]) and diabetic retinopathy (OR 0.40 [95% CI 0.16–0.99]), independently of age, sex, diabetes duration, A1c, hypertension, AER, eGFR, NT-proBNP, and TNF-α. Conclusions In this large cohort of DM1 patients, we reported an inverse and independent association of miR-146a-5p with diabetes chronic complications and in particular with CVD and retinopathy, suggesting that miR-146a-5p may be a novel candidate biomarker of DM1 complications.

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