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Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis

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 diff...

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Autores principales: Parkes, Joanna E., Rothwell, Simon, Oldroyd, Alexander, Chinoy, Hector, Lamb, Janine A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994128/
https://www.ncbi.nlm.nih.gov/pubmed/29884237
http://dx.doi.org/10.1186/s13075-018-1617-9
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author Parkes, Joanna E.
Rothwell, Simon
Oldroyd, Alexander
Chinoy, Hector
Lamb, Janine A.
author_facet Parkes, Joanna E.
Rothwell, Simon
Oldroyd, Alexander
Chinoy, Hector
Lamb, Janine A.
author_sort Parkes, Joanna E.
collection PubMed
description 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 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-018-1617-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-59941282018-06-21 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. Arthritis Res Ther Research Article 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 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-018-1617-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-08 2018 /pmc/articles/PMC5994128/ /pubmed/29884237 http://dx.doi.org/10.1186/s13075-018-1617-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Parkes, Joanna E.
Rothwell, Simon
Oldroyd, Alexander
Chinoy, Hector
Lamb, Janine A.
Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
title Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
title_full Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
title_fullStr Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
title_full_unstemmed Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
title_short Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
title_sort genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-tif1-γ autoantibodies in adult patients with myositis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994128/
https://www.ncbi.nlm.nih.gov/pubmed/29884237
http://dx.doi.org/10.1186/s13075-018-1617-9
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