Article: 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 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) 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.

Citing Articles

Understanding the Role of Type I Interferons in Cutaneous Lupus and Dermatomyositis: Toward Better Therapeutics.

Hile G, Werth V Arthritis Rheumatol. 2024; 77(1):1-11.

PMID: 39262215 PMC: 11685000. DOI: 10.1002/art.42983.

Sequence Alignment between Gene and Human Noncoding RNAs: A Potential Explanation for Paraneoplastic Dermatomyositis.

Talotta R J Pers Med. 2024; 14(6).

PMID: 38929849 PMC: 11204533. DOI: 10.3390/jpm14060628.

Polishing the crystal ball: mining multi-omics data in dermatomyositis.

Castillo R, Femia A Ann Transl Med. 2021; 9(5):435.

PMID: 33842656 PMC: 8033302. DOI: 10.21037/atm-20-5319.

Environmental triggers of dermatomyositis: a narrative review.

Bax C, Maddukuri S, Ravishankar A, Pappas-Taffer L, Werth V Ann Transl Med. 2021; 9(5):434.

PMID: 33842655 PMC: 8033368. DOI: 10.21037/atm-20-3719.

Genetics of idiopathic inflammatory myopathies: insights into disease pathogenesis.

Rothwell S, Chinoy H, Lamb J Curr Opin Rheumatol. 2019; 31(6):611-616.

PMID: 31415030 PMC: 6791565. DOI: 10.1097/BOR.0000000000000652.

References

1.

Burd C, Kinyamu H, Miller F, Archer T . UV radiation regulates Mi-2 through protein translation and stability. J Biol Chem. 2008; 283(50):34976-82. PMC: 2596409. DOI: 10.1074/jbc.M805383200. View

2.

Dourmishev L, Meffert H, Piazena H . Dermatomyositis: comparative studies of cutaneous photosensitivity in lupus erythematosus and normal subjects. Photodermatol Photoimmunol Photomed. 2004; 20(5):230-4. DOI: 10.1111/j.1600-0781.2004.00115.x. View

3.

Rothwell S, Cooper R, Lundberg I, Miller F, Gregersen P, Bowes J . Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups. Ann Rheum Dis. 2015; 75(8):1558-66. PMC: 5300750. DOI: 10.1136/annrheumdis-2015-208119. View

4.

Brouwer R, Hengstman G, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A . Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis. 2001; 60(2):116-23. PMC: 1753477. DOI: 10.1136/ard.60.2.116. View

5.

Gregersen P, Lee H, Batliwalla F, Begovich A . PTPN22: setting thresholds for autoimmunity. Semin Immunol. 2006; 18(4):214-23. DOI: 10.1016/j.smim.2006.03.009. View

6.

Cheong W, Hughes G, Norris P, Hawk J . Cutaneous photosensitivity in dermatomyositis. Br J Dermatol. 1994; 131(2):205-8. DOI: 10.1111/j.1365-2133.1994.tb08492.x. View

7.

Hengstman G, van Venrooij W, Vencovsky J, Moutsopoulos H, van Engelen B . The relative prevalence of dermatomyositis and polymyositis in Europe exhibits a latitudinal gradient. Ann Rheum Dis. 2000; 59(2):141-2. PMC: 1753065. DOI: 10.1136/ard.59.2.141. View

8.

Mathieu A, Cauli A, Fiorillo M, Sorrentino R . HLA-B27 and ankylosing spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis. Autoimmun Rev. 2008; 7(5):398-403. DOI: 10.1016/j.autrev.2008.03.013. View

9.

Matos T, Sheth V . The symbiosis of phototherapy and photoimmunology. Clin Dermatol. 2016; 34(5):538-47. DOI: 10.1016/j.clindermatol.2016.05.003. View

10.

Love L, Weinberg C, McConnaughey D, Oddis C, Medsger Jr T, Reveille J . Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women. Arthritis Rheum. 2009; 60(8):2499-504. PMC: 2855681. DOI: 10.1002/art.24702. View

11.

Okada S, Weatherhead E, Targoff I, Wesley R, Miller F . Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease. Arthritis Rheum. 2003; 48(8):2285-93. DOI: 10.1002/art.11090. View

Genetic Background May Contribute to the Latitude-dependent Prevalence of Dermatomyositis and Anti-TIF1-γ Autoantibodies in Adult Patients with Myositis