Calsequestrin as a risk factor in Graves’ hyperthyroidism and Graves’ ophthalmopathy patients

Abstract

Background: The pathogenesis of Graves’ ophthalmopathy (GO), Graves’ hyperthyroidism (GH) and the mechanisms for its link to thyroid autoimmunity are poorly understood. Our research focuses on the role of the skeletal muscle calcium binding protein calsequestrin (CASQ1) in thyroid. We measured the concentration of the CASQ1 protein correlating levels with parameters of the eye signs, CASQ1 antibody levels and CASQ1 gene polymorphism rs3838284. Methods: CASQ1 protein was measured by quantitative Western Blotting. The protein concentrations were expressed as pmol/mg total protein by reference to CASQ1 standards. Results: Western blot analysis showed the presence of two forms of CASQ1 in the thyroid. The mean concentration of CASQ1 protein was significantly reduced in patients with Graves’ disease, compared to thyroid from control subjects with multi-nodular goitre or thyroid cancer. Although in patients with GO it was lower than that, compared with patients with GH this difference was not significant. Reduced CASQ1 in Graves’ thyroid correlated with the homozygous genotype of the rs3838284 CASQ1 polymorphism. Conclusions: Decreased CASQ1 in the thyroid of patients with Graves’ disease compared to thyroid from control subjects is not explained but may reflect consumption of the protein during an autoimmune reaction against CASQ1 in the thyroid.