Asymptomatic Bilateral Internal Carotid Artery Occlusion with Ring Finger Protein 213 Gene Polymorphism

No abstract available.

Association between RNF213 rs6565666 polymorphism and intracranial cystic aneurysms in patients from Guangdong Province / 中华神经医学杂志

Objective To investigate the association between RNF213 rs6565666 polymorphisms and intracranial cystic aneurysms in patients from Guangdong province. Methods Two hundred and fifty patients with intracranial cystic aneurysms, admitted to and conformed by digital substraction angiography (DSA) in our hospital from February 2016 to October 2018, were selected as experimental group; and 250 patients without intracranial aneurysms conformed by DSA, CT angiography or magnetic resonance angiography at the same time period were used as control group. The genotypes of rs6565666 locus of RNF213 gene were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR). Results As compared with those in the control group, percentages of AG and AA genotypes were significantly higher and percentage of GG genotype was statistically higher at rs6565666 locus of patients from the experimental group (P<0.05). The proportion of allele A at rs6565666 locus in the experimental group was statistically higher as compared with that in the control group (P<0.05). In the experimental group, 112 patients had ruptured aneurysms and 138 patients did not have ruptured aneurysms; there was no statistically significant difference in the genotype distribution of rs6565666 between the ruptured group and the non-ruptured group (P>0.05). Conclusion RNF213 gene rs6565666 polymorphism is associated with intracranial cystic aneurysms in patients from Guangdong province.

RNF213 gene polymorphisms and susceptibility of intracranial vascular stenosis disease: a meta-analysis / 国际脑血管病杂志

Objective To investigate the correlation between RNF213 gene polymorphisms (rs112735431,rs138130613,and rs148731719) and the susceptibility of intracranial vascular stenosis disease.Methods The literature of studies on the correlation between RNF213 gene polymorphisms and intracranial vascular stenosis disease was collected according to the related databases.Using the Stata 12.0 software and selecting suitable genetic model,the heterogeneity was analyzed and the pooled odds ratio (OR) and its 95％ confidence interval (CI) were calculated.Results A total of 12 articles were included after screening.The result of meta-analysis showed that the rs112735431 polymorphism had a significant correlation with the susceptibility of moyamoya disease (MMD) in all genetic models,especially the most significant dominant model (AA + GA genotype vs.GG genotype:OR 101.46,95％ CI 59.41-173.27;P ＜0.001),at the same time,the polymorphism of this site also had significant correlation with the nonMMD intracranial large artery stenosis/occlusion (AA + GA genotype vs.GG genotype:OR 13.82,95％ CI 4.48-42.61;P＜ 0.001);the rs138130613 polymorphism had significant correlation with the susceptibility of MMD in Chinese population (OR 5.01,95％ CI 1.57-15.98;P=0.006);and no correlation between the rs148731719 polymorphism and the susceptibility of MMD was observed.Conclusions The RNF213 gene rs112735431 polymorphism is a susceptible factor of MMD,at the same time,the polymorphism of this site is also associated with the formation of non-MMD intracranial large artery stenosis.Systematic study on the molecular function of RNF213 may have important significance for diagnosis and treatment of such vascular stenosis diseases.

Moyamoya Disease: Cardiologist's Perspectives

Moyamoya disease (MMD) is a steno-occlusive disease of the cerebral artery around the circle of Willis. It was first described in 1957 in Japan and named because the characteristic appearance of the basal collaterals in cerebral angiography looks like “a puff of smoke” (moyamoya in Japanese). MMD is one of the major causes of stroke in children worldwide, however most common in Korea, Japan and China. In 2011 the ring finger protein 213 gene (RNF213) was identified as a susceptibility gene for MMD. The RNF213 R4810K variant is an Asian founder mutation common to above nations with carrier rates of 0.5-2% of the general population but a 1/150 penetrance of clinical MMD. MMD patients in Korea and Japan harbors RNF213 R4810K variant in 70-90%. In MMD arterial stenosis was found to occur systematically, not only in the intracranial cerebral arteries but also in renal, coronary, pulmonary arteries, suggesting that MMD is a systemic vasculopathy. These extracranial vasculopathy (ECV) is rare but important as a cause of renovascular hypertension, ischemic heart disease, and pulmonary hypertension especially in children with MMD or family members of MMD. Clinical features of ECV will be reviewed in this article.

Genetics and Biomarkers of Moyamoya Disease: Significance of RNF213 as a Susceptibility Gene / 대한뇌졸중학회지

Moyamoya disease is characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, recent genome-wide and locus-specific association studies identified RNF213 as an important susceptibility gene of moyamoya disease among East Asian population. A polymorphism in c.14576G>A in RNF213 was identified in 95% of familial patients with moyamoya disease and 79% of sporadic cases, and patients having this polymorphism were found to have significantly earlier disease onset and a more severe form of moyamoya disease, such as the presentation of cerebral infarction and posterior cerebral artery stenosis. The exact mechanism by which the RNF213 abnormality relates to moyamoya disease remains unknown, while recent reports using genetically engineered mice lacking RNF213 by homologous recombination provide new insight for the pathogenesis of this rare entity. Regarding biomarkers of moyamoya disease, moyamoya disease is characterized by an increased expression of angiogenic factors and pro-inflammatory molecules such as vascular endothelial growth factors and matrix metalloproteinase-9, which may partly explain its clinical manifestations of the pathologic angiogenesis, spontaneous hemorrhage, and higher incidence of cerebral hyperperfusion after revascularization surgery. More recently, blockade of these pro-inflammatory molecules during perioperative period is attempted to reduce the potential risk of surgical complication including cerebral hyperperfusion syndrome. In this review article, we focus on the genetics and biomarkers of moyamoya disease, and sought to discuss their clinical implication.