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

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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.

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Acknowledgments

This work was supported by: a) a grant from the “Associazione Nazionale Alopecia Areata“(ANAA); b) a grant from the “Compagnia di San Paolo“, Torino; c) a PRIN grant from the “Ministero dell’Istruzione, dell’Università e della Ricerca“(MIUR). However, the sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy

    G. Conteduca, A. Parodi, F. Ferrera, S. Tardito, F. Battaglia, F. Kalli, S. Negrini, F. Indiveri, D. Fenoglio & G. Filaci

  2. Department of Internal Medicine and Medical Specialities, “Sapienza” University of Rome, Rome, Italy

    A. Rossi

  3. Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy

    F. Megiorni & A. Pizzuti

  4. Associazione Nazionale Alopecia Areata, Genoa, Italy

    E. Rizza

  5. Department of Internal Medicine, University of Genoa, Genoa, Italy

    F. Indiveri, D. Fenoglio & G. Filaci

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  1. G. Conteduca
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  2. A. Rossi
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  3. F. Megiorni
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  4. A. Parodi
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  5. F. Ferrera
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  7. F. Battaglia
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  8. F. Kalli
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  10. A. Pizzuti
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  11. E. Rizza
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  14. G. Filaci
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Correspondence to G. Filaci.

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Conteduca, G., Rossi, A., Megiorni, F. et al. Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata. Clin Exp Med 14, 91–97 (2014). https://doi.org/10.1007/s10238-012-0224-3

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  • DOI: https://doi.org/10.1007/s10238-012-0224-3

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