Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1γ autoantibodies in adult myositis patients

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. This study investigated whether differing genetic background in populations could contribute to this distribution of DM. Methods Case data from the MYOGEN Immunochip study (n=1,769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n=9,911) were used to model the relationship of HLA associated with DM autoantibodies and DM or PM SNPs (suggestive significance in the Immunochip project p<2.25x10-5) in healthy controls with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for gender. Results The prevalence of DM, as a proportion of DM and PM combined, and the presence of 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 may contribute to the distribution of DM in addition to UV exposure.