TY - JOUR
T1 - Genome-Wide MicroRNA Analysis Implicates miR-30b/d in the Etiology of Alopecia Areata
AU - Tafazzoli, Aylar
AU - Forstner, Andreas J.
AU - Broadley, David
AU - Hofmann, Andrea
AU - Redler, Silke
AU - Petukhova, Lynn
AU - Giehl, Kathrin A.
AU - Kruse, Roland
AU - Blaumeiser, Bettina
AU - Böhm, Markus
AU - Bertolini, Marta
AU - Rossi, Alfredo
AU - Garcia Bartels, Natalie
AU - Lutz, Gerhard
AU - Wolff, Hans
AU - Blume-Peytavi, Ulrike
AU - Soreq, Hermona
AU - Christiano, Angela M.
AU - Botchkareva, Natalia V.
AU - Nöthen, Markus M.
AU - Betz, Regina C.
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042483958&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2017.09.046
DO - 10.1016/j.jid.2017.09.046
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C2 - 29080678
AN - SCOPUS:85042483958
SN - 0022-202X
VL - 138
SP - 549
EP - 556
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -
