TY - JOUR
T1 - Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis
AU - The Myositis Genetics Consortium (MYOGEN)
AU - Parkes, Joanna E.
AU - Rothwell, Simon
AU - Oldroyd, Alexander
AU - Chinoy, Hector
AU - Lamb, Janine A.
AU - Lundberg, Ingrid E.
AU - Miller, Frederick W.
AU - Cooper, Robert G.
AU - Ollier, William E.
AU - Gregersen, Peter K.
AU - Vencovsky, Jiri
AU - Danko, Katalin
AU - Limaye, Vidya
AU - Selva-O'Callaghan, Albert
AU - Machado, Pedro M.
AU - Hanna, Michael G.
AU - Platt, Hazel
AU - Molberg, Øyvind
AU - Benveniste, Olivier
AU - Radstake, Timothy
AU - De Bleecker, Jan
AU - De Paepe, Boel
AU - Maurer, Britta
AU - Padyukov, Leonid
AU - O'Hanlon, Terrance P.
AU - Wedderburn, Lucy R.
AU - Denton, Christopher
AU - Mann, Herman
AU - Hilton-Jones, David
AU - Kiely, Patrick
AU - Plotz, Paul H.
AU - Gourley, Mark
AU - Marder, Galina
AU - McHugh, Neil J.
AU - Betteridge, Zoe E.
PY - 2018/6/8
Y1 - 2018/6/8
N2 - 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.
AB - 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.
KW - Anti-Mi-2
KW - Anti-TIF1-γ
KW - Dermatomyositis
KW - Latitude
KW - Polymyositis
KW - Ultraviolet light
UR - http://www.scopus.com/inward/record.url?scp=85048288877&partnerID=8YFLogxK
U2 - 10.1186/s13075-018-1617-9
DO - 10.1186/s13075-018-1617-9
M3 - Article
C2 - 29884237
AN - SCOPUS:85048288877
VL - 20
SP - 117
JO - Arthritis Research & Therapy
JF - Arthritis Research & Therapy
SN - 1478-6362
IS - 1
M1 - 117
ER -