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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

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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 x 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-gamma) 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-gamma 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
Dermatomyositis, Polymyositis, Anti-TIF1-gamma, Anti-Mi-2, Latitude, Ultraviolet light, ULTRAVIOLET-RADIATION INTENSITY, CUTANEOUS PHOTOSENSITIVITY

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Chicago
Parkes, Joanna E, Simon Rothwell, Alexander Oldroyd, Hector Chinoy, Janine A Lamb, the Myositis Genetics Consortium (MYOGEN), Jan De Bleecker, and Boel De Paepe. 2018. “Genetic Background May Contribute to the Latitude-dependent Prevalence of Dermatomyositis and anti-TIF1-γ Autoantibodies in Adult Patients with Myositis.” Arthritis Research & Therapy 20.
APA
Parkes, J. E., Rothwell, S., Oldroyd, A., Chinoy, H., Lamb, J. A., Myositis Genetics Consortium (MYOGEN), the, De Bleecker, J., et al. (2018). Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis. ARTHRITIS RESEARCH & THERAPY, 20.
Vancouver
1.
Parkes JE, Rothwell S, Oldroyd A, Chinoy H, Lamb JA, Myositis Genetics Consortium (MYOGEN) the, et al. Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis. ARTHRITIS RESEARCH & THERAPY. 2018;20.
MLA
Parkes, Joanna E, Simon Rothwell, Alexander Oldroyd, et al. “Genetic Background May Contribute to the Latitude-dependent Prevalence of Dermatomyositis and anti-TIF1-γ Autoantibodies in Adult Patients with Myositis.” ARTHRITIS RESEARCH & THERAPY 20 (2018): n. pag. Print.
@article{8566167,
  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 {\textlangle} 2.25 x 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-gamma) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95\% CI 0.95-0.98, P {\textlangle} 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-gamma autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95\% CI 0.96-0.98, P {\textlangle} 0.001 and OR 0.98, 95\% CI 0.97-0.99, P {\textlangle} 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P {\textlangle} 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.},
  articleno    = {e117},
  author       = {Parkes, Joanna E and Rothwell, Simon and Oldroyd, Alexander and Chinoy, Hector and Lamb, Janine A and Myositis Genetics Consortium (MYOGEN), the and De Bleecker, Jan and De Paepe, Boel},
  issn         = {1478-6354},
  journal      = {ARTHRITIS RESEARCH \& THERAPY},
  keyword      = {Dermatomyositis,Polymyositis,Anti-TIF1-gamma,Anti-Mi-2,Latitude,Ultraviolet light,ULTRAVIOLET-RADIATION INTENSITY,CUTANEOUS PHOTOSENSITIVITY},
  language     = {eng},
  pages        = {5},
  title        = {Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-\ensuremath{\gamma} autoantibodies in adult patients with myositis},
  url          = {http://dx.doi.org/10.1186/s13075-018-1617-9},
  volume       = {20},
  year         = {2018},
}

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