Abstract

Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicle immunobiology. We evaluated, for the first time, the miR-17-92a-1 cluster host gene (MIR17HG) expression in peripheral blood of 248 unrelated alopecia areata (AA) patients compared to 244 matched controls using Real-Time qPCR. We also tested its association with different rs4284505A>G genotypes (based on TaqMan allelic discrimination PCR) and the available clinical data. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated for each genetic association model. The upregulation of miR-17 was observed in the serum of patients with alopecia compared to controls (p-value = 0.004). The ROC curve showed high diagnostic performance of miR-17 in differentiating between patients and controls (AUC = 0.85, p-value < 0.001). rs4284505*A/G heterozygotes were more susceptible to the disease (OR = 1.57, 95% CI = 1.01–2.45) under the over-dominant model. Interestingly, patients with the rs4284505*G/G genotype had a higher level of miR-17 than those with the A/A and A/G genotypes. The G/G genotype was associated with the severe phenotype (p-value = 0.038). A/G carriers were the youngest (p-value < 0.001), had more frequent scalp infection (p-value = 0.006), exhibited the worst dermatology life quality index score (p-value = 0.037), and responded less to treatment (p-value = 0.033). In conclusion, MIR17HG expression and the rs4284505 variant were significantly associated with AA and could play a role in pathogenesis and phenotype in the Egyptian population. Further multi-center studies in other ethnicities are warranted to replicate the findings.

Highlights

  • Alopecia areata (AA) is an autoimmune, non-scarring hair loss with the preservation of the hair follicle

  • The color code indicates the confidence level of abundance (D) gene ontology analysis of miR-17-92a-1 cluster host gene (MIR17HG). (E) Six microRNA cluster is involved in hair follicle-related biological processes. (F) Functional enrichment Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the six microRNAs within the

  • The genetic association models showed that A/A conferred protection against developing alopecia (OR = 0.51, 95% confidence interval (CI) = 0.27–0.96) under the recessive model, while heterozygote genotype (A/G) carriers were more susceptible to the disease (OR = 1.57, 95% CI = 1.01–2.45) under the overdominant model (Table 4)

Read more

Summary

Introduction

Alopecia areata (AA) is an autoimmune, non-scarring hair loss with the preservation of the hair follicle. This gene encodes four lncRNAs and one retained intron transcript by alternative splicing (www.ensembl.org, accessed on 25 August 2021), but only the longest is a polycistronic transcript containing the miR-17-92a-1 cluster (Figure 1). MicroRNAs originating from the post-transcriptional splicing of the MIR17HG were enriched in hair follicle-related pathways (Table S1). It was previously cited to be in linkage disequilibrium with an upstream polymorphism related to multiple sclerosis [16] and to be associated with systemic lupus erythematosus (SLE) [17] The impact of this polymorphism on AA susceptibility and phenotype has not been studied before, especially in the present population. In this sense, the authors were inspired to investigate the association of rs4284505 polymorphism in the MIR17HG gene cluster with AA risk and severity. The color code indicates the confidence level of abundance (D) gene ontology analysis of MIR17HG. (E) Six microRNA cluster is involved in hair follicle-related biological processes. (F) Functional enrichment KEGG pathway analysis for the six microRNAs within the MIR17HG cluster. [Data source: (www.ensembl.org), (http://diana.imis.athena-innovation.gr/), and (www.GeneCards.org) (all web sites are last accessed on 25 August 2021)]

Study Participants
Clinical Assessment
Allelic Discrimination of rs4284505 Variant
MIR17HG Expression Profiling
Statistical Analysis
Characteristics of the Study Population
Allelic Discrimination Analysis of rs4284505 SNP
Relative Expression of MIR17HG
Association
Discussion
Conclusions
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call