Single‐nucleotide polymorphisms in 3′‐untranslated region inducible costimulator gene and the important roles of miRNA in alopecia areata

Abstract Background Alopecia areata (AA) spares the stem cell compartment and attacks only the base of the hair follicle, which is surrounded by infiltrating lymphocytes. AA is associated with polymorphisms in immune‐related genes and with decreased function of CD4+CD25+ T regulatory (Treg) cells. Treg function is modulated by the costimulatory molecules, like inducible costimulator (ICOS) that are crucial in orienting T cell differentiation and function so that they strongly impact on the immunologic decision between tolerance or autoimmunity development. Objective The aim of our study was to investigate the possible association of AA with single‐nucleotide polymorphisms (SNP) present in the ICOS 3′‐untranslated region (3′UTR) region and to elucidate how SNPs modulate ICOS gene expression by affecting miRNA binding sites. Methods This is a case‐control study performed in 184 patients with AA and 200 controls. ICOS gene and miRNA expression were analyzed by real‐time polymerase chain reaction. Results The genotype carrying the rs4404254(C) [p = 0.012, OR (95% CI): 0.5 (0.3–0.8)] and rs4675379(C) [p = 0.015, OR (95% CI): 0.3 (0.1–0.8)] 3′ UTR alleles was more frequently observed in AA patients than in controls and correlated with a reduced ICOS expression. miR‐1276 significantly suppressed ICOS expression by binding to the 3′UTR of ICOS mRNA. Also, we observed that, miR‐101 and miR‐27b are upregulated, while miR‐103 and miR‐2355‐3p are downregulated in peripheral blood mononuclear cells of AA patients compared to controls; Conclusion Our data show that rs4404254 and rs4675379 SNPs of ICOS gene are associated with AA and also reveal that the presence of rs4404254 polymorphism correlates with ICOS post‐transcriptional repression by microRNA binding.

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