RNF213 rare variants and cerebral arteriovenous malformation in a Chinese population

Cerebral arteriovenous malformation (AVM) is characterised by an abnormal tangle of arteries and veins, the rupture of which is a significant portion of the morbidity and mortality cases, especially in young populations. However, the exact risk factors and pathophysiologic mechanisms of AVM remain poorly understood. RNF213 variants have been identified as obvious susceptible factors of several cerebrovascular disorders, such as Moyamoya disease and intracranial aneurysms. Thus, this study aimed to determine whether there is an association between RNF213 rare variants and AVM.

The AVM group included 22 patients with AVM. The control group included 1007 samples from the GeneSky in-house database and 208 samples from the 1000 Genome Project of Chinese Han Population. Genomic DNA samples were extracted from the peripheral blood of the AVM patients, and targeted exome sequencing of RNF213 was performed to assess the existence of low-frequency or rare variants. Sanger sequencing was performed to validate the identified variants. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the candidate variants and risk of AVM. Statistical analyses were performed using SPSS version 21.0.

The RNF213 c.10997T>C variant (amino acid mutation p.M3666T, NM_001256071) was observed in two AVM patients after filtration. It was significantly associated with AVM in the Chinese population (ORs, 10.30 and 25.08; 95 %; CIs, 1.38-77.10 and 4.34-144.90 compared with 1000 Genome Project of Chinese Han Population and GeneSky in-house database, respectively).

Rare variants of RNF213 are associated with AVM in the Chinese population, suggesting the important role of RNF213 in AVM. Further studies are needed to verify these findings.