| Summary: | The ring finger protein 213 gene (<i>RNF213</i>) encodes a 590 kDa protein that is thought to be involved in angiogenesis. This gene was first recognized as a vasculopathy-susceptibility locus through genome-wide association studies undertaken in a Japanese population, demonstrating that heterozygotes for <i>RNF213</i> p.Arg4810Lys (c.14429G>A, rs112735431) had a greatly increased risk of moyamoya disease. The association of <i>RNF213</i> p.Arg4810Lys as a susceptibility variant of moyamoya disease was reproduced in Korean and Chinese individuals and, later, in Caucasians. Variants of the <i>RNF213</i> gene have been linked to a number of vascular diseases such as moyamoya disease, intracranial major artery stenosis, pulmonary arterial hypertension, and peripheral pulmonary artery stenosis, and have also been associated with co-occurrent diseases and vascular disease in different organs. Based on the findings that we have reported to date, our paper proposes a new concept of “<i>RNF213</i>-associated vascular disease” to unify these conditions with the aim of capturing patients with multiple diseases but with a common genetic background. This concept will be highly desirable for clarifying all of the diseases in the <i>RNF213</i>-associated vascular disease category by means of global epidemiological investigations because of the possibility of such diseases appearing asymptomatically in some patients.
|
|---|