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

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.

Associations between alopecia areata and multiple sclerosis: a report of two cases and review of the literature

“…In AA, three genome‐wide association studies showed that 12 independent genetic loci, including loci encoding genes in both innate and adaptive immunity, are involved. In particular, among the HLA class II genes, the DR4, DR5, DQ3, DQ7, and DPW4 alleles are strongly associated . Similarly, MS shows strong association with more than 100 polymorphisms; most of them are related to immune function genes, particularly linked to the major histocompatibility complex (MHC) II allele HLA‐DR2 …”

“…In particular, among the HLA class II genes, the DR4, DR5, DQ3, DQ7, and DPW4 alleles are strongly associated. 10,11 Similarly, MS shows strong association with more than 100 polymorphisms; most of them are related to immune function genes, particularly linked to the major histocompatibility complex (MHC) II allele HLA-DR2. 12 Another common aspect between AA and MS concerns the environmental factors that may cause the onset of the autoimmune activation.…”

A “hair‐raising” history of alopecia areata

“…Our understanding of AA pathogenesis has advanced significantly, though it still has many gaps. Today, AA research is active in genetics, the microbiome, the role of the environment, the role of atopy, immune cell types in AA pathogenesis, primary antigenic targets, mechanisms by which immune cells influence hair follicles, and of course the development of new treatments based on these discoveries. This increased AA research activity (Figure ), from a larger number of professionals, promises momentous developments to come!…”

Italian Guidelines in diagnosis and treatment of alopecia areata

“…in particular, among the Hla class ii genes the dr4, dr5, dQ3, dQ7 and dPW4 alleles are strongly associated. 17,18 interestingly an increased risk for autoimmune type…”