Circulating TGF-β1-Regulated miRNAs and the Risk of Rapid Progression to ESRD in Type 1 Diabetes.
We investigated whether circulating TGF-β1-regulated miRNAs detectable in plasma are associated with the risk of rapid progression to end-stage renal disease (ESRD) in a cohort of proteinuric patients with type 1 diabetes (T1D) and normal eGFR. Plasma specimens obtained at entry to the study were examined in two prospective subgroups that were followed for 7-20 years (rapid progressors and nonprogressors), as well as a reference panel of normoalbuminuric T1D patients. Of the five miRNAs examined in this study, let-7c-5p and miR-29a-3p were significantly associated with protection against rapid progression and let-7b-5p and miR-21-5p were significantly associated with the increased risk of ESRD. In logistic analysis, controlling for HbA1c and other covariates, let-7c-5p and miR-29a-3p were associated with more than a 50% reduction in the risk of rapid progression (P ≤ 0.001), while let-7b-5p and miR-21-5p were associated with a >2.5-fold increase in the risk of ESRD (P ≤ 0.005). This study is the first prospective study to demonstrate that circulating TGF-β1-regulated miRNAs are deregulated early in T1D patients who are at risk for rapid progression to ESRD.
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA.
Marcus G
MG
Pezzolesi
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA.
Eiichiro
E
Satake
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.
Kevin P
KP
McDonnell
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.
Melissa
M
Major
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA.
Adam M
AM
Smiles
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA Department of Medicine, Harvard Medical School, Boston, MA andrzej.krolewski@joslin.harvard.edu.
Andrzej S
AS
Krolewski
D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011507:Proteinuria / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C524940:MIRN21 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C487931:mirnlet7 microRNA, human