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Association of Ring Finger Protein 213 Gene P.R4810k Polymorphism with Intracranial Major Artery Stenosis/Occlusion

  • Author Footnotes
    1 These authors contributed equally to this work.
    Qian Zhang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Lebao Yu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Peicong Ge
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Yonggang Ma
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Dong Zhang
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Yan Zhang
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Rong Wang
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Shuo Wang
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Yuanli Zhao
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Yong Cao
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Xingju Liu
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Xiaofeng Deng
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Jizong Zhao
    Correspondence
    Address correspondence to Jizong Zhao, MD, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantanxili, DongCheng District, Beijing 100050 China.
    Affiliations
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    China National Clinical Research Center for Neurological Diseases, Beijing, China

    Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China

    Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Background

      Intracranial major artery stenosis/occlusion (ICASO) is a common cause of ischemic stroke worldwide. A number of studies have assessed the association of the p.R4810K polymorphism in the ring finger protein 213 (RNF213) gene with ICASO, but the results have not been entirely consistent.

      Methods

      We conducted a case-control study to estimate the association between the p.R4810K polymorphism and the risk of ICASO in a Chinese population. A total of 124 patients and 230 controls were enrolled. Moreover, a meta-analysis was performed to evaluate this association in the East Asian populations.

      Results

      In our case-control study, the frequencies of the G/A genotype of p.R4810K were significantly higher in the ICASO patients than in the control group (4.03% versus .43%, P = .021, respectively). Moreover, in the meta-analysis, we assessed 7 case-control studies that included 1239 patients and 1377 controls. The pooled odds ratios (ORs) indicated significant association between the p.R4810K polymorphism and the ICASO risk in the dominant model (OR = 9.37, 95% confidence interval: 4.61-19.02, P = .000), the heterozygote comparison (OR = 8.97, 95% CI: 4.41-18.25, P = .000), and the allele comparison (OR = 9.50, 95% confidence interval: 4.71-19.19, P = .000) in the East Asian populations. Subgroup analysis based on ethnicity revealed that the risks in the Japanese and the Korean populations were higher than that in the Chinese population.

      Conclusions

      The p.R4810K polymorphism was associated with an increased risk of ICASO in the East Asian populations. Further studies on the function of the RNF213 protein and the clinical features of this subtype of ICASO are needed.

      Key Words

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      References

        • Gorelick P.B.
        • Wong K.S.
        • Bae H.J.
        • et al.
        Large artery intracranial occlusive disease: a large worldwide burden but a relatively neglected frontier.
        Stroke. 2008; 39: 2396-2399
        • Banerjee C.
        • Chimowitz M.I.
        Stroke caused by atherosclerosis of the major intracranial arteries.
        Circ Res. 2017; 120: 502-513
        • Kim J.S.
        • Kim Y.J.
        • Ahn S.H.
        • et al.
        Location of cerebral atherosclerosis: why is there a difference between East and West?.
        Int J Stroke. 2016; (Epub ahead of print)
        • Ikram M.A.
        • Seshadri S.
        • Bis J.C.
        • et al.
        Genomewide association studies of stroke.
        N Engl J Med. 2009; 360: 1718-1728
        • Liu W.
        • Morito D.
        • Takashima S.
        • et al.
        Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development.
        PLoS ONE. 2011; 6 (e22542)
        • Kamada F.
        • Aoki Y.
        • Narisawa A.
        • et al.
        A genome-wide association study identifies RNF213 as the first Moyamoya disease gene.
        J Hum Genet. 2011; 56: 34-40
        • Miyawaki S.
        • Imai H.
        • Takayanagi S.
        • et al.
        Identification of a genetic variant common to moyamoya disease and intracranial major artery stenosis/occlusion.
        Stroke. 2012; 43: 3371-3374
        • Morimoto T.
        • Mineharu Y.
        • Ono K.
        • et al.
        Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease.
        PLoS ONE. 2017; 12 (e0175649)
        • Zhou S.
        • Ambalavanan A.
        • Rochefort D.
        • et al.
        RNF213 is associated with intracranial aneurysms in the French-Canadian population.
        Am J Hum Genet. 2016; 99: 1072-1085
        • Koizumi A.
        • Kobayashi H.
        • Liu W.
        • et al.
        P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure.
        Environ Health Prev Med. 2013; 18: 121-129
        • Miyatake S.
        • Miyake N.
        • Touho H.
        • et al.
        Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease.
        Neurology. 2012; 78: 803-810
        • Park M.G.
        • Shin J.H.
        • Lee S.W.
        • et al.
        RNF213 rs112735431 polymorphism in intracranial artery steno-occlusive disease and moyamoya disease in Koreans.
        J Neurol Sci. 2017; 375: 331-334
        • Shang D.
        • Shi C.
        • Mao C.
        • et al.
        Association between ring finger protein 213 gene polymorphism and ischemic stroke in a Chinese Han population.
        J Apoplexy Nerv Dis. 2015; 32 (in Chinese): 594-597
        • Huang Y.
        • Cheng D.
        • Zhang J.
        • et al.
        Association between RNF213 gene polymorphisms and the genetic susceptibility of adult Moyamoya disease of Zhuang population in Guangxi.
        J Apoplexy Nerv Dis. 2015; 32 (in Chinese): 918-921
        • Zhang T.
        • Guo C.
        • Liao X.
        • et al.
        Genetic analysis of RNF213 p.R4810K variant in non-moyamoya intracranial artery stenosis/occlusion disease in a Chinese population.
        Environ Health Prev Med. 2017; 22: 1-7
        • Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis
        • Health Labour Sciences Research Grant for Research on Measures for Infractable Diseases
        Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis).
        Neurol Med Chir (Tokyo). 2012; 52: 245-266
        • Zhang Q.
        • Liu Y.
        • Zhang D.
        • et al.
        RNF213 as the major susceptibility gene for Chinese patients with moyamoya disease and its clinical relevance.
        J Neurosurg. 2017; 126: 1106-1113
        • Harbord R.M.
        • Egger M.
        • Sterne J.A.
        A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints.
        Stat Med. 2006; 25: 3443-3457
        • Miyawaki S.
        • Imai H.
        • Shimizu M.
        • et al.
        Genetic variant RNF213 c.14576G>A in various phenotypes of intracranial major artery stenosis/occlusion.
        Stroke. 2013; 44: 2894-2897
        • Kim Y.J.
        • Lee J.K.
        • Ahn S.H.
        • et al.
        Nonatheroscleotic isolated middle cerebral artery disease may be early manifestation of moyamoya disease.
        Stroke. 2016; 47: 2229-2235
        • Bang O.Y.
        • Chung J.W.
        • Cha J.
        • et al.
        A polymorphism in RNF213 is a susceptibility gene for intracranial atherosclerosis.
        PLoS ONE. 2016; 11 (e0156607)
        • Liu W.
        • Hitomi T.
        • Kobayashi H.
        • et al.
        Distribution of moyamoya disease susceptibility polymorphism p.R4810K in RNF213 in East and Southeast Asian populations.
        Neurol Med Chir (Tokyo). 2012; 52: 299-303
        • Miao W.
        • Zhao P.L.
        • Zhang Y.S.
        • et al.
        Epidemiological and clinical features of Moyamoya disease in Nanjing, China.
        Clin Neurol Neurosurg. 2010; 112: 199-203
        • Kuriyama S.
        • Kusaka Y.
        • Fujimura M.
        • et al.
        Prevalence and clinicoepidemiological features of moyamoya disease in Japan: findings from a nationwide epidemiological survey.
        Stroke. 2008; 39: 42-47
        • Ahn I.M.
        • Park D.H.
        • Hann H.J.
        • et al.
        Incidence, prevalence, and survival of moyamoya disease in Korea: a nationwide, population-based study.
        Stroke. 2014; 45: 1090-1095
        • Hitomi T.
        • Habu T.
        • Kobayashi H.
        • et al.
        Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from moyamoya patients.
        Biochem Biophys Res Commun. 2013; 438: 13-19
        • Ito A.
        • Fujimura M.
        • Niizuma K.
        • et al.
        Enhanced post-ischemic angiogenesis in mice lacking RNF213; a susceptibility gene for moyamoya disease.
        Brain Res. 2015; 1594: 310-320
        • Kanoke A.
        • Fujimura M.
        • Niizuma K.
        • et al.
        Temporal profile of the vascular anatomy evaluated by 9.4-tesla magnetic resonance angiography and histological analysis in mice with the R4859K mutation of RNF213, the susceptibility gene for moyamoya disease.
        Brain Res. 2015; 1624: 497-505
        • Matsuda Y.
        • Mineharu Y.
        • Kimura M.
        • et al.
        RNF213 p.R4810K variant and intracranial arterial stenosis or occlusion in relatives of patients with moyamoya disease.
        J Stroke Cerebrovasc Dis. 2017; 26: 1841-1847
        • Bang O.Y.
        • Ryoo S.
        • Kim S.J.
        • et al.
        Adult moyamoya disease: a burden of intracranial stenosis in East Asians?.
        PLoS ONE. 2015; 10 (e0130663)