title: Decreased expression of circulating microRNA-126 in patients with type 2 diabetic nephropathy: A potential blood-based biomarker.
abstract: Circulating microRNAs (miRNAs) have been proposed as promising biomarkers for multiple diseases. miR-126 is reported to be associated with type 2 diabetes mellitus (T2D), diabetic nephropathy (DN) and end stage renal disease. The aim of this study was to investigate the expression of circulating miR-126 and to assess its potential as a blood-based biomarker for DN in T2D patients. In 52 patients with T2D without history of DN (with noromoalbuminuria), 50 patients with T2D and DN (29 with microalbuminuria and 21 with macroalbuminuria), and 50 non-diabetic healthy controls, the expression of circulating miR-126 in peripheral whole blood was evaluated by quantitative polymerase chain reaction. The expression levels of circulating miR-126 were significantly decreased in T2D patients and further decreased in DN patients compared with those in the controls. Multivariate logistic regression analysis confirmed the independent association of lower miR-126 levels with T2D [adjusted odds ratio (OR), 0.797; 95% confidence interval (CI), 0.613-0.960] and DN (adjusted OR, 0.513; 95% CI, 0.371-0.708). miR-126 levels were associated with the degree of albuminuria and showed significantly low expression in DN patients with microalbuminuria (adjusted OR, 0.781; 95% CI; 0.698-0.952) and further lower expression in DN patients with macroalbuminuria (adjusted OR, 0.433; 95% CI, 0.299-0.701), respectively compared with T2D patients with normoalbuminuria. miR-126 levels negatively correlated with albuminuria positively with glomerular filtration rate (P<0.05), and in addition, negatively correlated with fasting glucose, glycated hemoglobin, triglyceride and LDL (P<0.05). Stepwise multiple regression analysis identified albuminuria as a significant predictor of miR-126 (P<0.001). miR-126 in peripheral blood yielded area under the receiver operating characteristic curves of 0.854 (95% CI, 0.779-0.929) and 0.959 (95% CI, 0.916-1.000) in the differentiation of DN patients from T2D patients and DN patients from non-diabetic controls respectively. These data suggest that decreased expression of circulating miR-126 is associated with the development of DN in T2D patients, and may be a promising blood-based biomarker for DN risk estimation.
authors.affiliation: Department of Molecular Medicine/Al-Jawhara Centre for Molecular Medicine, Genetics and Inherited Disorders, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 26671, Kingdom of Bahrain.
authors.forename: Ghada
authors.initials: G
authors.lastname: Al-Kafaji
authors.affiliation: Diabetes and Endocrinology Clinic, Salmaniya Medical Complex, Manama 12, Kingdom of Bahrain.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Al-Mahroos
authors.affiliation: Department of Molecular Medicine/Al-Jawhara Centre for Molecular Medicine, Genetics and Inherited Disorders, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 26671, Kingdom of Bahrain.
authors.forename: Haifa Abdulla
authors.initials: HA
authors.lastname: Al-Muhtaresh
authors.affiliation: Department of Molecular Medicine/Al-Jawhara Centre for Molecular Medicine, Genetics and Inherited Disorders, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 26671, Kingdom of Bahrain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Skrypnyk
authors.affiliation: Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 26671, Kingdom of Bahrain.
authors.forename: Mohamed Abdalla
authors.initials: MA
authors.lastname: Sabry
authors.affiliation: Department of Life Sciences, Medical Biotechnology, College of Graduate Studies, Arabian Gulf University, Manama 26671, Kingdom of Bahrain.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Ramadan
keywords: biomarker; circulating miRNAs; diabetic nephropathy; miR-126; type 2 diabetes mellitus