title: MicroRNA-224 is Readily Detectable in Urine of Individuals with Diabetes Mellitus and is a Potential Indicator of Beta-Cell Demise.
abstract: MicroRNA (miRNA) are a class of non-coding, 19-25 nucleotide RNA critical for network-level regulation of gene expression. miRNA serve as paracrine signaling molecules. Using an unbiased array approach, we previously identified elevated levels of miR-224 and miR-103 to be associated with a monogenic form of diabetes; HNF1A-MODY. miR-224 is a novel miRNA in the field of diabetes. We sought to explore the role of miR-224 as a potential biomarker in diabetes, and whether such diabetes-associated-miRNA can also be detected in the urine of patients. Absolute levels of miR-224 and miR-103 were determined in the urine of n = 144 individuals including carriers of a HNF1A mutation, participants with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and normal controls. Expression levels were correlated with clinical and biochemical parameters. miR-224 was significantly elevated in the urine of carriers of a HNF1A mutation and participants with T1DM. miR-103 was highly expressed in urine across all diabetes cohorts when compared to controls. For both miR-224 and-103, we found a significant correlation between serum and urine levels (p < 0.01). We demonstrate that miRNA can be readily detected in the urine independent of clinical indices of renal dysfunction. We surmise that the differential expression levels of miR-224 in both HNF1A-MODY mutation carriers and T1DM may be an attempt to compensate for beta-cell demise.
authors.affiliation: Department of Endocrinology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. siobhanbacon@gmail.com.
authors.forename: Siobhán
authors.initials: S
authors.lastname: Bacon
authors.affiliation: Departments of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. brittaengelbrecht@gmx.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Engelbrecht
authors.affiliation: Departments of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. jasmin.schmid@gmail.com.|Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. jasmin.schmid@gmail.com.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Schmid
authors.affiliation: Departments of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. shonapfeiffer@rcsi.ie.
authors.forename: Shona
authors.initials: S
authors.lastname: Pfeiffer
authors.affiliation: Departments of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. rossgallagher@rcsi.ie.
authors.forename: Ross
authors.initials: R
authors.lastname: Gallagher
authors.affiliation: Department of Endocrinology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. ailbhe.mccarthy@gmail.com.
authors.forename: Ailbhe
authors.initials: A
authors.lastname: McCarthy
authors.affiliation: Department of Endocrinology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. mbyrne@mater.ie.
authors.forename: Marie
authors.initials: M
authors.lastname: Burke
authors.affiliation: Departments of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. cconcannon@rcsi.ie.|Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. cconcannon@rcsi.ie.
authors.forename: Caoimhín
authors.initials: C
authors.lastname: Concannon
authors.affiliation: Departments of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. prehn@rcsi.ie.|Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. prehn@rcsi.ie.
authors.forename: Jochen H M
authors.initials: JH
authors.lastname: Prehn
authors.affiliation: Department of Endocrinology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. mbyrne@mater.ie.|Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. mbyrne@mater.ie.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Byrne
keywords: diabetes associated microRNA; insulin secretion; miR-103; miR-224; urinary biomarker