RNF213 c.14429G > A (p.Arg4810Lys) is associated with non-arteritic retinal artery occlusion.

Retinal artery occlusion (RAO) results in severe visual impairment and may indicate cerebral infarction and extracranial carotid artery stenosis at onset. RAO-related genetic factors remain understudied. We investigated the association between RAO and RNF213 p.Arg4810Lys (c.14429G > A), a genetic variant recently identified as a susceptibility factor for moyamoya disease, a risk factor for stroke. Patients diagnosed with non-arteritic (NA)-RAO at our department between May 2020 and April 2021 underwent magnetic resonance imaging and computed tomography angiography. Sanger sequencing revealed that RNF213 p.Arg4810Lys was significantly more frequent in the NA-RAO group (10.7%) than in the control group (1.1%). We conducted a logistic regression analysis adjusted for age and sex to compare the NA-RAO (n = 28) and healthy control groups (n = 1,202), which indicated a significant association between RNF213 p.Arg4810Lys and NA-RAO (P = 0.001, odds ratio 13.52, 95% confidence interval [3.09-59.18]). Among patients with NA-RAO, 50%, 76%, and 40% had simultaneous strokes, hypertension, and diabetes, respectively. There were no significant differences between groups in medical history, biomarkers, imaging characteristics, or ophthalmic artery diameter. RNF213 p.Arg4810Lys was significantly associated with NA-RAO, indicating genetic susceptibility to systemic vascular diseases. Further studies can elucidate broader implications of RNF213 p.Arg4810Lys in vascular disease pathogenesis, particularly in East Asian populations.