Pandora L Wander1, Daniel A Enquobahrie2, Theo K Bammler3, James W MacDonald3, Sengkeo Srinouanprachanh3, Thanmai Kaleru4, Dori Khakpour4, Subbulaxmi Trikudanathan4. 1. Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States; Division of General Internal Medicine, University of Washington, Seattle, WA, United States. Electronic address: lwander@u.washington.edu. 2. Department of Epidemiology, University of Washington, Seattle, WA, United States. 3. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States. 4. Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA, United States.
Abstract
BACKGROUND: Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS. METHODS: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR)-adjusted cutoff p < 0.1 to correct for multiple testing. We used miRDB's Gene Ontology (GO) tool to identify predicted pathways for top hits. RESULTS: Mean age and BMI of participants were 27.9 years and 32.5 kg/m2, respectively. Lower levels of miR-1294 were associated with higher waist circumference (β = -0.10, FDR = 0.095). While no miRNAs were associated with HOMA-IR at our FDR cut off <0.1, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at unadjusted p < 0.01, including members of the highly conserved miR-17/92 cluster and miR-1294 (β = -0.10, p < 0.001). The GO analysis of miR-1294 identified 54 overrepresented pathways, including "negative regulation of insulin receptor signaling" (FDR = 0.019), and 6 underrepresented pathways. CONCLUSIONS: Plasma miR-1294 along with members of the miR-17/92 cluster and miRNAs involved in insulin signaling may be associated with central obesity and insulin resistance in PCOS. Larger studies among women with and without PCOS are needed to validate these findings. Published by Elsevier B.V.
BACKGROUND: Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS. METHODS: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR)-adjusted cutoff p < 0.1 to correct for multiple testing. We used miRDB's Gene Ontology (GO) tool to identify predicted pathways for top hits. RESULTS: Mean age and BMI of participants were 27.9 years and 32.5 kg/m2, respectively. Lower levels of miR-1294 were associated with higher waist circumference (β = -0.10, FDR = 0.095). While no miRNAs were associated with HOMA-IR at our FDR cut off <0.1, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at unadjusted p < 0.01, including members of the highly conserved miR-17/92 cluster and miR-1294 (β = -0.10, p < 0.001). The GO analysis of miR-1294 identified 54 overrepresented pathways, including "negative regulation of insulin receptor signaling" (FDR = 0.019), and 6 underrepresented pathways. CONCLUSIONS: Plasma miR-1294 along with members of the miR-17/92 cluster and miRNAs involved in insulin signaling may be associated with central obesity and insulin resistance in PCOS. Larger studies among women with and without PCOS are needed to validate these findings. Published by Elsevier B.V.
Authors: Daniel A Dumesic; Sharon E Oberfield; Elisabet Stener-Victorin; John C Marshall; Joop S Laven; Richard S Legro Journal: Endocr Rev Date: 2015-10 Impact factor: 19.871
Authors: Mora Murri; María Insenser; Elena Fernández-Durán; José L San-Millán; Manuel Luque-Ramírez; Héctor F Escobar-Morreale Journal: Metabolism Date: 2018-02-02 Impact factor: 8.694
Authors: Anja E Sørensen; Pernille B Udesen; Grzegorz Maciag; Julian Geiger; Negar Saliani; Andrzej S Januszewski; Guozhi Jiang; Ronald C Ma; Anandwardhan A Hardikar; Marie Louise M Wissing; Anne Lis M Englund; Louise T Dalgaard Journal: Front Med (Lausanne) Date: 2019-11-01
Authors: Christian Wake; Adam Labadorf; Alexandra Dumitriu; Andrew G Hoss; Joli Bregu; Kenneth H Albrecht; Anita L DeStefano; Richard H Myers Journal: BMC Genomics Date: 2016-10-04 Impact factor: 3.969
Authors: Rosa Jiménez-Lucena; Antonio Camargo; Juan Francisco Alcalá-Diaz; Cristina Romero-Baldonado; Raúl Miguel Luque; Ben van Ommen; Javier Delgado-Lista; Jose María Ordovás; Pablo Pérez-Martínez; Oriol Alberto Rangel-Zúñiga; Jose López-Miranda Journal: Exp Mol Med Date: 2018-12-26 Impact factor: 8.718