The Association of the RNF213 p.R4810K Polymorphism with Quasi-Moyamoya Disease and a Review of the Pertinent Literature

Abstract

Background: Quasi-moyamoya disease (MMD) is characterized by moyamoya vasculopathy and well-recognized comorbidity. Whether the recently identified MMD susceptibility gene variant, p.R4810K (rs112735431), is associated with quasi-MMD remains unclear.

Methods: This study was a 2-hospital-based case-control study that was conducted in the neurosurgical departments of Beijing Tiantan Hospital and Peking University International Hospital. A total of 42 patients and 161 controls were enrolled. The p.R4810K polymorphism was assessed with Sanger sequencing. A review of the pertinent literature on the p.R4810K polymorphism and quasi-MMD was performed.

Results: The mean age of patients at diagnosis was 34.9 ± 16.5 years with a one-peak distribution in the forties; 57.1% of the patients were female. The p.R4810K heterozygous variant was identified in 5 patients, including 3 patients with atherosclerosis, 1 patient with Graves disease, and 1 patient with rheumatoid arthritis; it was also observed in one control. The frequencies of the A allele and the G/A genotype of rs112735431 (p.R4810K) were significantly greater in the patients with quasi-MMD than in the control groups (5.95% vs. 0.31%, odds ratio [OR] 20.316, P = 0.002; 11.9% vs. 0.6%, OR 21.622, P = 0.002, respectively). In the subgroup analysis, the rs112735431 G/A genotype was significantly associated with arteriosclerotic or autoimmune quasi-MMD (P = 0.006, OR 25.263, confidence interval 2.501-255.175; P = 0.015, OR 29.091, confidence interval 2.444-346.334, respectively).

Conclusions: The p.R4810K variant was associated with atherosclerotic and autoimmune quasi-MMD in a Chinese population, and a lower prevalence of this variant in patients with quasi-MMD compared with patients with MMD was observed.

Keywords: Atherosclerosis; Clinical features; Quasi-moyamoya disease; RNF213; p.R4810K.