BACKGROUND: Alopecia areata (AA) is the second most common cause of hair loss in humans, and has a genetically complex inheritance. The hypothesis that AA is autoimmune in nature is supported by previous studies. These report an association with specific HLA alleles, as well as genetic variants of other genes implicated in autoimmunity, such as various cytokine genes. However, these cannot yet be considered proven susceptibility loci, as many of these association findings were derived from small patient samples. OBJECTIVES: To investigate the association between AA and selected cytokine genes using a sample of 768 patients with AA and 658 controls of Central European origin. METHODS: Eleven single-nucleotide polymorphisms (SNPs) from cytokine genes implicated in previous AA studies were genotyped. These genes were IL1B, IL1A, IL1RN, MIF, IFNG and the TNF/LTA gene region. We also genotyped 15 SNPs selected from cytokine genes that have shown significant association with other autoimmune diseases. These genes were IL10, IL36RN, IL12B, IL6, IL2, IL23, IL2RA and IL4R. RESULTS: Significant association was found for two variants within both IL2RA and TNF/LTA. In the overall sample, the most significant results were obtained for the IL2RA variant rs706778 (P = 0·00038) and the TNF/LTA locus variant rs1800629 (P = 0·0017). In subgroup analyses, according to severity, age at onset and family history these effects were stronger in the severely affected patients, with the lowest P-values being obtained for rs706778 (P = 3·8 × 10(-6) ). CONCLUSIONS: Our results point to the involvement of IL2RA and the TNF/LTA region in the aetiology of AA, in particular severe AA, and provide further support for the hypothesis that AA is autoimmune in nature.
BACKGROUND:Alopecia areata (AA) is the second most common cause of hair loss in humans, and has a genetically complex inheritance. The hypothesis that AA is autoimmune in nature is supported by previous studies. These report an association with specific HLA alleles, as well as genetic variants of other genes implicated in autoimmunity, such as various cytokine genes. However, these cannot yet be considered proven susceptibility loci, as many of these association findings were derived from small patient samples. OBJECTIVES: To investigate the association between AA and selected cytokine genes using a sample of 768 patients with AA and 658 controls of Central European origin. METHODS: Eleven single-nucleotide polymorphisms (SNPs) from cytokine genes implicated in previous AA studies were genotyped. These genes were IL1B, IL1A, IL1RN, MIF, IFNG and the TNF/LTA gene region. We also genotyped 15 SNPs selected from cytokine genes that have shown significant association with other autoimmune diseases. These genes were IL10, IL36RN, IL12B, IL6, IL2, IL23, IL2RA and IL4R. RESULTS: Significant association was found for two variants within both IL2RA and TNF/LTA. In the overall sample, the most significant results were obtained for the IL2RA variant rs706778 (P = 0·00038) and the TNF/LTA locus variant rs1800629 (P = 0·0017). In subgroup analyses, according to severity, age at onset and family history these effects were stronger in the severely affected patients, with the lowest P-values being obtained for rs706778 (P = 3·8 × 10(-6) ). CONCLUSIONS: Our results point to the involvement of IL2RA and the TNF/LTA region in the aetiology of AA, in particular severe AA, and provide further support for the hypothesis that AA is autoimmune in nature.
Authors: Silke Redler; Marina Angisch; Stefanie Heilmann; Sabrina Wolf; Sandra Barth; Buket F Basmanav; Kathrin A Giehl; Sandra Hanneken; Sibylle Eigelshoven; Elisabeth Mangold; Roland Kruse; Bettina Blaumeiser; Markus Böhm; Michael Knapp; Natalie Garcia Bartels; Gerhard Lutz; Hans Wolff; Ulrike Blume-Peytavi; Markus M Nöthen; Tim Becker; Regina C Betz Journal: J Invest Dermatol Date: 2014-10-22 Impact factor: 8.551
Authors: K J McElwee; A Gilhar; D J Tobin; Y Ramot; J P Sundberg; M Nakamura; M Bertolini; S Inui; Y Tokura; L E King; B Duque-Estrada; A Tosti; A Keren; S Itami; Y Shoenfeld; A Zlotogorski; R Paus Journal: Exp Dermatol Date: 2013-09 Impact factor: 3.960
Authors: Regina C Betz; Lynn Petukhova; Stephan Ripke; Hailiang Huang; Androniki Menelaou; Silke Redler; Tim Becker; Stefanie Heilmann; Tarek Yamany; Madeliene Duvic; Maria Hordinsky; David Norris; Vera H Price; Julian Mackay-Wiggan; Annemieke de Jong; Gina M DeStefano; Susanne Moebus; Markus Böhm; Ulrike Blume-Peytavi; Hans Wolff; Gerhard Lutz; Roland Kruse; Li Bian; Christopher I Amos; Annette Lee; Peter K Gregersen; Bettina Blaumeiser; David Altshuler; Raphael Clynes; Paul I W de Bakker; Markus M Nöthen; Mark J Daly; Angela M Christiano Journal: Nat Commun Date: 2015-01-22 Impact factor: 14.919
Authors: Katarzyna Tabara; Magdalena Kozłowska; Anna Jędrowiak; Wojciech Bienias; Andrzej Kaszuba Journal: Postepy Dermatol Alergol Date: 2019-02-22 Impact factor: 1.837