Abstract TMP101: Relationship Between RNF213 p.R4810K (c.14429G>A) Variant and Anatomical Variations of the Circle of Willis

Abstract

Background and purpose: RING finger protein 213 ( RNF213 ) gene is strongly associated with intracranial arterial stenosis as well as Moyamoya disease and its dysregulation is known to impair cerebral perfusion in rodents. We thus investigated the relationship between RNF213 p.R4810K (c.14429G>A) variant and the anatomical variations of the circle of Willis in cerebrovascular disease. Methods: We consecutively enrolled non-cardioembolic stroke or transient ischemic attack patients with (n = 20) or without (n = 80) RNF213 p.R4810K (c.14429G>A) variation from those who participated in the biobank of our Institute over the past 2 years. Moyamoya disease cases were excluded. We evaluated anatomical variations of the vessels constituting the circle of the Willis, namely, intracranial internal carotid artery, anterior communicating artery (AcomA), anterior cerebral artery A1 segment, posterior communicating artery (PcomA), posterior cerebral artery P1 segment, and middle cerebral artery M1 segment, using maximum intensity projection of a time-of-flight magnetic resonance angiography collected at 3 Tesla. Results: The RNF213 p.R4810K (c.14429G>A) variant carrier had higher frequency of focal narrowing of the M1 segment compared to the non-carrier (50% vs 10%, p<0.01) and an absence of AcomA (15% vs 3.7%, p=0.09). By contrast, unexpectedly, unilateral or bilateral absence of PcomA was significantly less frequent (25% vs 61%, p<0.01). Multivariate analysis adjusted for age and sex showed that the variant carrier state was independently associated with unilateral or bilateral presence of PcomA (odds ratio (OR) 4.44, 95% confidence interval (CI) 1.01 - 20.6, p<0.05) and focal M1 narrowing (OR 3.30, 95% CI 0.82 - 12.6, p=0.09). Conclusions: The RNF 213 p.R4810K (c.14429G>A) variant carrier showed higher frequency of arteriopathy in the anterior circulation accompanied by higher patency rate of PcomA. In the variant carrier, dysplasia of the anterior circulation arteries may lead to compensatory collateral flow from posterior to anterior circulation through PcomA.