Abstract WP182: Association Of The RNF213 p.R4810k Variant With Thyroid Disease And Autoantibodies In Ischemic Stroke

Background: Thyroid diseases and elevated thyroid autoantibodies are associated with moyamoya disease (MMD). MMD susceptibility variant RNF213 p.R4810K is known to increase the risk of ischemic stroke (IS), but whether thyroid diseases and thyroid autoantibody levels are altered in IS patients carrying the RNF213 p.R4810K variant remains elusive. Methods: Of the consecutive adult IS patients from 2011 to 2020 admitted in our institute, patients who signed a consent form for RNF213 genotyping were included, while definitive MMD patients were excluded. We compared the patient background, history of thyroid disease (hyperthyroidism or hypothyroidism), and levels of serum triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), antithyroperoxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb) between the variant carrier and non-carrier. Each thyroid autoantibody was measured by the electro-chemiluminescent immunoassay method. Results: Of the 1570 patients (525 women; 72 years of median age) analyzed, 74 (4.7%) patients had the RNF213 p.R4810K variant. The variant carriers were more likely to be female (52.7% vs. 35.3%, P <0.01), younger (58 years vs. 73 years, P <0.01), and have a history of hypothyroidism (18.9% vs. 1.8%, P =0.01), middle cerebral artery M1 stenosis (29.7% vs. 6.0%, P =0.01), and large-artery atherosclerosis (47.3% vs. 25.0%, P <0.01) than the variant non-carriers. Both mean TPOAb (17.60 IU/mL vs. 3.96 IU/mL, P <0.01) and TgAb levels (25.09 IU/mL vs. 15.64 IU/mL, P <0.01) were higher in the variant carriers, and there were no inter-group differences for history of hyperthyroidism, TSH, free T3/T4, and administration of levothyroxine sodium hydrate. A multivariate regression analysis showed that hypothyroidism(odds ratio [OR], 8.30; 95% confidential interval [CI], 2.83-24.33) and the elevated TPOAb levels (OR per 1 IU/mL increment, 3.32; 95% CI, 1.43-7.78) were independently associated with variant carriers versus non-carriers. Conclusions: Hypothyroidism and elevated TPOAb levels were frequently observed in IS patients with the RNF213 p.R4810K variant, which may be associated with immune aberrancies relevant to or underlying thyroid autoimmunity, contributing to the different features of IS.