[Pathophysiology of RNF213-related Vasculopathy]

The p.R4810K variant of the RNF213 gene was identified as the founder variant of East Asian moyamoya disease. The association of the p.R4810K variant with non-moyamoya intracranial arterial stenosis has been demonstrated, and the concept of RNF213-related vasculopathy has been proposed, suggesting a continuous spectrum of moyamoya disease. Additionally, moyamoya disease is occasionally accompanied by polyvascular disease involving intracranial and neck vessels, coronary arteries(especially vasospastic angina), pulmonary arteries, aorta, abdominal visceral arteries, and peripheral arteries, which are associated with RNF213 variants, mainly p.R4810K. The severity of vascular diseases caused by the RNF213 variant is inconsistent, and some environmental and genetic factors are believed to jointly define the phenotype. RNF213 variants confer the greatest risk of cardiovascular diseases in East Asia. Therefore, successful targeting of these variants is essential for controlling cardiovascular diseases, including stroke, in East Asian countries.