Investigation of selected cytokine genes suggests that IL2RA and the TNF/LTA locus are risk factors for severe alopecia areata
S. Redler
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Search for more papers by this authorF. Albert
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Search for more papers by this authorF.F. Brockschmidt
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
Search for more papers by this authorC. Herold
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorS. Hanneken
Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorS. Eigelshoven
Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorK.A. Giehl
Department of Dermatology, University of Munich, Munich, Germany
Search for more papers by this authorG. Lutz
Dermatological Practice, Hair & Nail, Wesseling, Germany
Search for more papers by this authorH. Wolff
Department of Dermatology, University of Munich, Munich, Germany
Search for more papers by this authorB. Blaumeiser
Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium
Search for more papers by this authorM. Böhm
Department of Dermatology, University of Münster, Münster, Germany
Search for more papers by this authorT. Becker
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
Search for more papers by this authorM.M. Nöthen
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
Search for more papers by this authorR.C. Betz
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Search for more papers by this authorS. Redler
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Search for more papers by this authorF. Albert
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Search for more papers by this authorF.F. Brockschmidt
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
Search for more papers by this authorC. Herold
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorS. Hanneken
Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorS. Eigelshoven
Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorK.A. Giehl
Department of Dermatology, University of Munich, Munich, Germany
Search for more papers by this authorG. Lutz
Dermatological Practice, Hair & Nail, Wesseling, Germany
Search for more papers by this authorH. Wolff
Department of Dermatology, University of Munich, Munich, Germany
Search for more papers by this authorB. Blaumeiser
Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium
Search for more papers by this authorM. Böhm
Department of Dermatology, University of Münster, Münster, Germany
Search for more papers by this authorT. Becker
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
Search for more papers by this authorM.M. Nöthen
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
Search for more papers by this authorR.C. Betz
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
Search for more papers by this authorFunding sources: German Research Foundation (DFG) and BONFOR program of the Medical faculity of the University of Bonn.
Conflicts of interest: None declared.
The first two authors contributed equally to this work.
Summary
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.
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