Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

Abstract

Alopecia areata (AA), an autoimmune disease affecting anagen stage hair follicles, is associated with polymorphisms in immune-related genes and with decreased number of CD4? CD25? T regulatory cells (Treg). Treg function is modulated by the forkhead box protein 3 (FOXP3) transcription factor and by inducible costimulator (ICOS), through interaction with the relative ligand, ICOSLG, whose genes are polymorphic. The aim of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) of the rs2294020 FOXP3 and/ or rs378299 ICOSLG genes may be associated with AA. A case-control study was performed in 120 AA patients and 84 controls. SNPs were analyzed by gene sequencing. FOXP3 and ICOSLG gene expressions were analyzed by real-time PCR. Increased frequencies of the genotype carrying the FOXP3 rs2294020-3675(A) [P = 0.002, OR (95 % CI): 2.55 (1.2-2.7)] or the ICOSLG rs378299-509(C) [P = 0.01, OR (95 % CI): 2.21 (1.1-2.6)] allelic variants were observed in AA patients than in controls. The genotype carrying the combination of the FOXP3 rs2294020-3675(A) and ICOSLG rs378299-509(C) allelic variants with the HLA DQB1*03 allele was more frequently present in AA patients than in controls (P = 0.04). The presence of the FOXP3 rs2294020-3675(A) or the I-COSLG rs378299-509(C) allelic variant was associated with reduced relative gene expression in AA patients. These data suggest that rs2294020 SNP of FOXP3 gene and rs378299 SNP of ICOSLG gene are associated with AA and with a reduced expression of the FOXP3 and ICOSLG genes in alopecia patients.

The role of lymphocytes in the development and treatment of alopecia areata

“…Although overall Foxp3 + Treg numbers seem to be normal in PBMC populations of AA patients, their function is impaired [99,118]. SNPs in the promoter regions of gene Foxp3 and gene ICOSLG (inducible T-cell co-stimulator ligand) which affects Treg functions have been associated with a reduced expression of the FOXP3 and ICOSLG genes in AA patients [119]. It has recently been shown that cutaneous memory Tregs (mTregs) reside in human skin which have unique cell surface marker expression and cytokine production [120].…”

Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune diseases with focus on systemic lupus erythematosus

“…systemic lupus erythematosus, psoriasis and vitiligo. Moreover, the occurrence of this SNP has been shown, by other authors, to be associated with susceptibility to alopecia aerata [12]. It would be interesting to investigate in the near future the possible pathogenetic mechanisms underlying these skin-related autoimmune disorders.…”

“…rs2294020 has been investigated in juvenile idiopathic arthritis [10], hay fever [11], and alopecia areata [12]. In particular, Eastell et al [10], found no association between FOXP3 rs2294020 polymorphism and juvenile idiopathic arthritis in a case-control association analysis of a UK population, although the authors did not rule out FOXP3 as a candidate gene for this disease, due to the low statistical power obtained in male enrolled patients.…”

“…The occurrence of the SNP rs2294020 also slightly increased the risk for atopy [11]. Alopecia areata, an autoimmune disorder, has been shown to be associated with the rs2294020 polymorphism in an Italian population [12]. …”

A case with Turner syndrome and alopecia areata

“…Alopesi Areata (AA), değişik şekil ve büyüklükte olabilen, deride iz bırakmayan saç, kirpik, kaş, sakal, bıyık ya da vücudun diğer bölgelerindeki kılların yama biçimli dökülmesiyle karakterize otoimmün bir hastalıktır. AA her iki cinsiyeti de etkileyebilen bir hastalıktır ve dünya genelinde görülme sıklığı yaklaşık %1-2'dir [3]. AA'da saç kaybının olduğu alanlarda deri normal görünümdedir.…”