Ioanna Kokkinopoulou1, Eirini Maratou2, Panayota Mitrou3, Eleni Boutati2, Diamantis C Sideris4, Emmanuel G Fragoulis4, Maria-Ioanna Christodoulou5,6. 1. Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece. iwanna-k@biol.uoa.gr. 2. Second Department of Internal Medicine and Research Institute, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, Greece. 3. Ministry of Health, Athens, Greece. 4. Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece. 5. Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece. mchrist@biol.uoa.gr. 6. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. mchrist@biol.uoa.gr.
Abstract
AIM: Certain microRNA molecules (miRNAs) that target genes involved in beta-cell growth and insulin resistance are found deregulated in patients with type-2 diabetes mellitus (T2D) and correlate with its complications. However, the expression profile of miRNAs that regulate genes bearing T2D-related single-nucleotide polymorphisms has been hardly studied. We recently reported that the mRNA patterns of specific T2D-susceptibility genes are impaired in patients, and associate with disease parameters and risk factors. The aim of this study was to explore the levels of miRNAs that target those genes, in peripheral blood of patients versus controls. METHODS: A panel of 14 miRNAs validated to target the CDKN2A, CDK5, IGF2BP2, KCNQ1, and TSPAN8 genes, was developed upon combined search throughout the DIANNA TarBase v7.0, miRTarBase, miRSearch v3.0-Exiqon, miRGator v3.0, and miRTarget Link Human algorithms. Specifically developed poly(A)polyadenylation(PAP)-reverse transcription(RT)-qPCR protocols were applied in peripheral blood RNA samples from patients and controls. Possible correlations with the disease, clinicopathological parameters and/or risk factors were evaluated. RESULTS: T2D patients expressed decreased levels of let-7b-5p, miR-1-3p, miR-24-3p, miR-34a-5p, miR-98-5p, and miR-133a-3p, compared with controls. Moreover, these levels correlated with certain disease features including insulin and % HbA1c levels in patients, as well as BMI, triglycerides' levels and family history in controls. CONCLUSIONS: A T2D-specific expression profile of miRNAs that target disease-susceptibility genes is for the first time described. Future studies are needed to elucidate the associated transcription-regulatory mechanisms, perchance involved in T2D pathogenesis, and to evaluate the potential of these molecules as possible biomarkers for this disorder.
AIM: Certain microRNA molecules (miRNAs) that target genes involved in beta-cell growth and insulin resistance are found deregulated in patients with type-2 diabetes mellitus (T2D) and correlate with its complications. However, the expression profile of miRNAs that regulate genes bearing T2D-related single-nucleotide polymorphisms has been hardly studied. We recently reported that the mRNA patterns of specific T2D-susceptibility genes are impaired in patients, and associate with disease parameters and risk factors. The aim of this study was to explore the levels of miRNAs that target those genes, in peripheral blood of patients versus controls. METHODS: A panel of 14 miRNAs validated to target the CDKN2A, CDK5, IGF2BP2, KCNQ1, and TSPAN8 genes, was developed upon combined search throughout the DIANNA TarBase v7.0, miRTarBase, miRSearch v3.0-Exiqon, miRGator v3.0, and miRTarget Link Human algorithms. Specifically developed poly(A)polyadenylation(PAP)-reverse transcription(RT)-qPCR protocols were applied in peripheral blood RNA samples from patients and controls. Possible correlations with the disease, clinicopathological parameters and/or risk factors were evaluated. RESULTS:T2Dpatients expressed decreased levels of let-7b-5p, miR-1-3p, miR-24-3p, miR-34a-5p, miR-98-5p, and miR-133a-3p, compared with controls. Moreover, these levels correlated with certain disease features including insulin and % HbA1c levels in patients, as well as BMI, triglycerides' levels and family history in controls. CONCLUSIONS: A T2D-specific expression profile of miRNAs that target disease-susceptibility genes is for the first time described. Future studies are needed to elucidate the associated transcription-regulatory mechanisms, perchance involved in T2D pathogenesis, and to evaluate the potential of these molecules as possible biomarkers for this disorder.
Authors: Damian Szklarczyk; Andrea Franceschini; Stefan Wyder; Kristoffer Forslund; Davide Heller; Jaime Huerta-Cepas; Milan Simonovic; Alexander Roth; Alberto Santos; Kalliopi P Tsafou; Michael Kuhn; Peer Bork; Lars J Jensen; Christian von Mering Journal: Nucleic Acids Res Date: 2014-10-28 Impact factor: 16.971
Authors: Andrew P Morris; Benjamin F Voight; Tanya M Teslovich; Teresa Ferreira; Ayellet V Segrè; Valgerdur Steinthorsdottir; Rona J Strawbridge; Hassan Khan; Harald Grallert; Anubha Mahajan; Inga Prokopenko; Hyun Min Kang; Christian Dina; Tonu Esko; Ross M Fraser; Stavroula Kanoni; Ashish Kumar; Vasiliki Lagou; Claudia Langenberg; Jian'an Luan; Cecilia M Lindgren; Martina Müller-Nurasyid; Sonali Pechlivanis; N William Rayner; Laura J Scott; Steven Wiltshire; Loic Yengo; Leena Kinnunen; Elizabeth J Rossin; Soumya Raychaudhuri; Andrew D Johnson; Antigone S Dimas; Ruth J F Loos; Sailaja Vedantam; Han Chen; Jose C Florez; Caroline Fox; Ching-Ti Liu; Denis Rybin; David J Couper; Wen Hong L Kao; Man Li; Marilyn C Cornelis; Peter Kraft; Qi Sun; Rob M van Dam; Heather M Stringham; Peter S Chines; Krista Fischer; Pierre Fontanillas; Oddgeir L Holmen; Sarah E Hunt; Anne U Jackson; Augustine Kong; Robert Lawrence; Julia Meyer; John R B Perry; Carl G P Platou; Simon Potter; Emil Rehnberg; Neil Robertson; Suthesh Sivapalaratnam; Alena Stančáková; Kathleen Stirrups; Gudmar Thorleifsson; Emmi Tikkanen; Andrew R Wood; Peter Almgren; Mustafa Atalay; Rafn Benediktsson; Lori L Bonnycastle; Noël Burtt; Jason Carey; Guillaume Charpentier; Andrew T Crenshaw; Alex S F Doney; Mozhgan Dorkhan; Sarah Edkins; Valur Emilsson; Elodie Eury; Tom Forsen; Karl Gertow; Bruna Gigante; George B Grant; Christopher J Groves; Candace Guiducci; Christian Herder; Astradur B Hreidarsson; Jennie Hui; Alan James; Anna Jonsson; Wolfgang Rathmann; Norman Klopp; Jasmina Kravic; Kaarel Krjutškov; Cordelia Langford; Karin Leander; Eero Lindholm; Stéphane Lobbens; Satu Männistö; Ghazala Mirza; Thomas W Mühleisen; Bill Musk; Melissa Parkin; Loukianos Rallidis; Jouko Saramies; Bengt Sennblad; Sonia Shah; Gunnar Sigurðsson; Angela Silveira; Gerald Steinbach; Barbara Thorand; Joseph Trakalo; Fabrizio Veglia; Roman Wennauer; Wendy Winckler; Delilah Zabaneh; Harry Campbell; Cornelia van Duijn; Andre G Uitterlinden; Albert Hofman; Eric Sijbrands; Goncalo R Abecasis; Katharine R Owen; Eleftheria Zeggini; Mieke D Trip; Nita G Forouhi; Ann-Christine Syvänen; Johan G Eriksson; Leena Peltonen; Markus M Nöthen; Beverley Balkau; Colin N A Palmer; Valeriya Lyssenko; Tiinamaija Tuomi; Bo Isomaa; David J Hunter; Lu Qi; Alan R Shuldiner; Michael Roden; Ines Barroso; Tom Wilsgaard; John Beilby; Kees Hovingh; Jackie F Price; James F Wilson; Rainer Rauramaa; Timo A Lakka; Lars Lind; George Dedoussis; Inger Njølstad; Nancy L Pedersen; Kay-Tee Khaw; Nicholas J Wareham; Sirkka M Keinanen-Kiukaanniemi; Timo E Saaristo; Eeva Korpi-Hyövälti; Juha Saltevo; Markku Laakso; Johanna Kuusisto; Andres Metspalu; Francis S Collins; Karen L Mohlke; Richard N Bergman; Jaakko Tuomilehto; Bernhard O Boehm; Christian Gieger; Kristian Hveem; Stephane Cauchi; Philippe Froguel; Damiano Baldassarre; Elena Tremoli; Steve E Humphries; Danish Saleheen; John Danesh; Erik Ingelsson; Samuli Ripatti; Veikko Salomaa; Raimund Erbel; Karl-Heinz Jöckel; Susanne Moebus; Annette Peters; Thomas Illig; Ulf de Faire; Anders Hamsten; Andrew D Morris; Peter J Donnelly; Timothy M Frayling; Andrew T Hattersley; Eric Boerwinkle; Olle Melander; Sekar Kathiresan; Peter M Nilsson; Panos Deloukas; Unnur Thorsteinsdottir; Leif C Groop; Kari Stefansson; Frank Hu; James S Pankow; Josée Dupuis; James B Meigs; David Altshuler; Michael Boehnke; Mark I McCarthy Journal: Nat Genet Date: 2012-08-12 Impact factor: 38.330