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

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 i...

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Autores principales: 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
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Publicado: BMC 2021
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spelling oai:doaj.org-article:b0a7a980d04c4a2db4937bdfa7a3c4552021-11-28T12:06:48ZMicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS10.1186/s12967-021-03142-41479-5876https://doaj.org/article/b0a7a980d04c4a2db4937bdfa7a3c4552021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03142-4https://doaj.org/toc/1479-5876Abstract 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.Federica BaruttaBeatrice CorbettaStefania BelliniSimonetta GuarreraGiuseppe MatulloMichela ScandellaCasper SchalkwijkCoen D. StehouwerNish ChaturvediSabita S. Soedamah-MuthuMarilena DurazzoGabriella GrudenBMCarticleMicroRNAsType 1 diabetesRetinopathyCardiovascular diseasesMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic MicroRNAs
Type 1 diabetes
Retinopathy
Cardiovascular diseases
Medicine
R
spellingShingle MicroRNAs
Type 1 diabetes
Retinopathy
Cardiovascular diseases
Medicine
R
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
MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
description 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.
format article
author 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
author_facet 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
author_sort Federica Barutta
title MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
title_short MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
title_full MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
title_fullStr MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
title_full_unstemmed MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
title_sort microrna 146a is associated with diabetic complications in type 1 diabetic patients from the eurodiab pcs
publisher BMC
publishDate 2021
url https://doaj.org/article/b0a7a980d04c4a2db4937bdfa7a3c455
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