title: 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 ICOSLG 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.
authors.affiliation: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Conteduca
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.forename: F
authors.initials: F
authors.lastname: Megiorni
authors.forename: A
authors.initials: A
authors.lastname: Parodi
authors.forename: F
authors.initials: F
authors.lastname: Ferrera
authors.forename: S
authors.initials: S
authors.lastname: Tardito
authors.forename: F
authors.initials: F
authors.lastname: Battaglia
authors.forename: F
authors.initials: F
authors.lastname: Kalli
authors.forename: S
authors.initials: S
authors.lastname: Negrini
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: E
authors.initials: E
authors.lastname: Rizza
authors.forename: F
authors.initials: F
authors.lastname: Indiveri
authors.forename: D
authors.initials: D
authors.lastname: Fenoglio
authors.forename: G
authors.initials: G
authors.lastname: Filaci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000506:Alopecia Areata / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020869:Gene Expression Profiling; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand