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Arthritis Res Ther. 2018 Jun 8;20(1):117. doi: 10.1186/s13075-018-1617-9.

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

Author information

1
Centre for Epidemiology, Division of Population Health, Health Services Research & Primary Care, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, 2.706 Stopford Building, Oxford Road, Manchester, M13 9PT, UK. joanna.parkes@postgrad.manchester.ac.uk.
2
Centre for Musculoskeletal Research, Division of Musculoskeletal & Dermatological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
3
Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
4
National Institute for Health Research Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
5
Department of Rheumatology, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK.
6
Centre for Epidemiology, Division of Population Health, Health Services Research & Primary Care, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, 2.706 Stopford Building, Oxford Road, Manchester, M13 9PT, UK.

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 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.

KEYWORDS:

Anti-Mi-2; Anti-TIF1-γ; Dermatomyositis; Latitude; Polymyositis; Ultraviolet light

PMID:
29884237
PMCID:
PMC5994128
DOI:
10.1186/s13075-018-1617-9
[Indexed for MEDLINE]
Free PMC Article

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