Frequency of the moyamoya-related RNF213 p.Arg4810Lys variant in 1,516 Korean individuals

Background: Moyamoya disease (MMD) is a progressive steno-occlusive vasculopathy that involves large intracranial arteries accompanied by abnormal collateral vessels. Recently, RNF213 was identified as a susceptibility gene for MMD and p.Arg4810Lys (rs112735431) is the most common variant in East Asian MMD patients. Interestingly, many studies have reported that a certain proportion of the general population in Japan, Korea, and China also has this variant. In this study, we investigated the frequency of this variant and estimated an odds ratio of MMD using two different Korean populations. Methods: A total of 1,516 anonymous DNA samples, 799 from an umbilical cord blood bank and 717 from routine health-checked adults, were genotyped using targeted Sanger sequencing. Results: The p. Arg4810Lys variant was detected at genotype frequencies of 2.25 % (18/799; 95 % confidence interval (CI), 1.43-3.53 %) in cord blood samples and 2.65 % (19/717; 95 % CI, 1.70-4.10 %) in adult samples, respectively. This variant showed a strong association with MMD (P < 0.001), giving an odds ratio of 162.7 (95 % CI, 65.5-403.9) and 137.8 (95 % CI, 55.8-339.9) based on the cord blood and adults samples, respectively. Conclusions: These results confirm that the RNF213 p. Arg4810Lys variant is not uncommon in the general Korean population and provide reference data for the association of this variant and MMD.