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J Invest Dermatol. 2018 Mar;138(3):549-556. doi: 10.1016/j.jid.2017.09.046. Epub 2017 Dec 6.

Genome-Wide MicroRNA Analysis Implicates miR-30b/d in the Etiology of Alopecia Areata.

Author information

1
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
2
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany; Department of Psychiatry (UPK), University of Basel, Basel, Switzerland; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
3
Centre for Skin Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK.
4
Institute of Human Genetics, University of Bonn, Bonn, Germany; Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany.
5
Department of Dermatology, Columbia University, New York, New York, USA; Department of Epidemiology, Columbia University, New York, New York, USA.
6
Department of Dermatology, University of Munich, Munich, Germany.
7
Dermatological Practice, Paderborn, Germany.
8
Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium.
9
Department of Dermatology, University of Münster, Münster, Germany.
10
Department of Internal Medicine and Medical Specialties, University of La Sapienza, Rome, Italy.
11
Clinical Research Center for Hair and Skin Science, Department for Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
12
Hair and Nail, Dermatological Practice, Wesseling, Germany.
13
The Edmond and Lily Safra Center of Brain Science and the Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
14
Department of Dermatology, Columbia University, New York, New York, USA.
15
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. Electronic address: regina.betz@uni-bonn.de.

Abstract

Alopecia areata (AA) is one of the most common forms of human hair loss. Although genetic studies have implicated autoimmune processes in AA etiology, understanding of the etiopathogenesis is incomplete. Recent research has implicated microRNAs, a class of small noncoding RNAs, in diverse autoimmune diseases. To our knowledge, no study has investigated the role of microRNAs in AA. In this study, gene-based analyses were performed for microRNAs using data of the largest genome-wide association meta-analysis of AA to date. Nominally, significant P-values were obtained for 78 of the 617 investigated microRNAs. After correction for multiple testing, three of the 78 microRNAs remained significant. Of these, miR-30b/d was the most significant microRNA for the follow-up analyses, which also showed lower expression in the hair follicle of AA patients. Target gene analyses for the three microRNAs showed 42 significantly associated target genes. These included IL2RA, TNXB, and ERBB3, which had been identified as susceptibility loci in previous genome-wide association studies. Using luciferase assay, site-specific miR-30b regulation of the AA risk genes IL2RA, STX17, and TNXB was validated. This study implicates microRNAs in the pathogenesis of AA. This finding may facilitate the development of future treatment strategies.

PMID:
29080678
DOI:
10.1016/j.jid.2017.09.046

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