Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
Parkes, Joanna E.; Rothwell, Simon; Oldroyd, Alexander; Chinoy, Hector; Lamb, Janine A.; Lundberg, Ingrid E.; Miller, Frederick W.; Cooper, Robert G.; Ollier, William E.; Gregersen, Peter K.; Vencovsky, Jiri; Danko, Katalin; Limaye, Vidya; Selva-O'Callaghan, Albert; Machado, Pedro M.; Hanna, Michael G.; Platt, Hazel; Molberg, Øyvind; Benveniste, Olivier; Radstake, Timothy; De Bleecker, Jan; De Paepe, Boel; Maurer, Britta; Padyukov, Leonid; O'Hanlon, Terrance P.; Wedderburn, Lucy R.; Denton, Christopher; Mann, Herman; Hilton-Jones, David; Kiely, Patrick; Plotz, Paul H.; Gourley, Mark; Marder, Galina; McHugh, Neil J.; Betteridge, Zoe E.; The Myositis Genetics Consortium (MYOGEN)
(2018) Arthritis Research and Therapy, volume 20, issue 1
(Article)
Abstract
Background: The prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to
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this distribution of DM. Methods: Case data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n = 1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n = 9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P < 2.25 × 10- 5) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex. Results: The prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-γ) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95-0.98, P < 0.001; and OR 0.95, 95% CI 0.92-0.99, P = 0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-γ autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96-0.98, P < 0.001 and OR 0.98, 95% CI 0.97-0.99, P < 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P < 0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes. Conclusions: These results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.
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Keywords: Anti-Mi-2, Anti-TIF1-γ, Dermatomyositis, Latitude, Polymyositis, Ultraviolet light, Rheumatology, Immunology and Allergy, Immunology
ISSN: 1478-6354
Publisher: BioMed Central
Note: Funding Information: This study was supported by Myositis UK, Medical Research Council (MRC) UK grant MR/N003322/1; Arthritis Research UK (18474), Association Francaise Contre Les Myopathies (AFM), the European Union Sixth Framework Programme (project AutoCure; LSH-018661), the European Science Foundation (ESF) within the framework of the Research Networking Programme European Myositis Network (EUMYONET), the Swedish Research Council and the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, and the intramural research program of the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH). The Czech cohort was supported by Project for Conceptual Development of Research Organization 00023728 from the Ministry of Health in the Czech Republic. JEP is supported by a University of Manchester alumni “Research Impact” doctoral studentship and president’s doctoral scholar award. This report includes description of independent research supported by the National Institute for Health Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. Publisher Copyright: © 2018 The Author(s).
(Peer reviewed)
