AUTHOR=Eto Futoshi , Yoshimoto Takeshi , Okazaki Shuhei , Nishimura Kunihiro , Ogura Shiori , Yamaguchi Eriko , Fukuma Kazuki , Saito Satoshi , Washida Kazuo , Koga Masatoshi , Toyoda Kazunori , Morimoto Takaaki , Maruyama Hirofumi , Koizumi Akio , Ihara Masafumi 

TITLE=RNF213 p.R4810K (c.14429G > A) Variant Determines Anatomical Variations of the Circle of Willis in Cerebrovascular Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.681743

DOI=10.3389/fnagi.2021.681743

ISSN=1663-4365

ABSTRACT=<sec><title>Introduction</title><p>Dysregulation of the RING finger protein 213 <italic>(RNF213)</italic> gene impairs vascular formation in experimental animal models. In addition, vascular abnormalities in the circle of Willis are associated with cerebrovascular disease. Here, we evaluated the relationship between the East Asian founder variant <italic>RNF213</italic> p.R4810K and consequent anatomical variations in the circle of Willis in cerebrovascular disease.</p></sec><sec><title>Patients and Methods</title><p>The present study is an observational cross-sectional study. It included patients with acute anterior circulation non-cardioembolic stroke admitted to our institution within 7 days of symptom onset or last-known-well from 2011 to 2019, and those who participated in the National Cerebral and Cardiovascular Center Biobank. We compared anatomical variations of the vessels constituting the circle of Willis between <italic>RNF213</italic> p.R4810K (c.14429G &gt; A) variant carriers and non-carriers using magnetic resonance angiography and assessed the association between the variants and the presence of the vessels constituting the circle of Willis. Patients with moyamoya disease were excluded.</p></sec><sec><title>Results</title><p>Four hundred eighty-one patients [146 women (30%); median age 70 years; median baseline National Institutes of Health Stroke Scale score 5] were analyzed. The <italic>RNF213</italic> p.R4810K variant carriers (<italic>n</italic> = 25) were more likely to have both posterior communicating arteries (PComAs) than the variant non-carriers (<italic>n</italic> = 456) (56% vs. 13%, <italic>P</italic> &lt; 0.01). Furthermore, variant carriers were less likely to have an anterior communicating artery (AComA) than non-carriers (68% vs. 84%, <italic>P</italic> = 0.04). In a multivariate logistic regression analysis, the association of <italic>RNF213</italic> p.R4810K variant carriers with the presence of both PComAs and the absence of AComA remained significant.</p></sec><sec><title>Conclusion</title><p>Our findings suggest that the <italic>RNF213</italic> p.R4810K variant is an important factor in determining anatomical variations in the circle of Willis.</p></sec>