Genetic Factor for Intracranial Artery Stenosis

Abstract

  Intracranial artery stenosis (ICAS), one of the major causes of ischemic stroke, has been suggested to have a genetic factor due to its high prevalence among Asians. We have identified a missense variant c.14429G＞A (p.Arg4810Lys, rs112735431) of Ringer finger protein 213 (RNF213), which had originally been identified as a susceptibility genetic variant for moyamoya disease, to be significantly associated with ICAS. Furthermore, we conducted a comprehensive search for variants of RNF213 other than p.Arg4810Lys in ICAS. p.Arg4810Lys was the only variant that had a significant association with ICAS. Moreover, various rare variants of RNF213 were found in the ICAS cohort. Therefore, functional analysis of RNF213 is indispensable to clarify whether these rare variants are truly associated with the onset of ICAS. RNF213 p.Arg4810Lys has been shown to be associated not only with ICAS/moyamoya disease but also with coronary stenosis/renal artery stenosis and pulmonary hypertension. RNF213 p.Arg4810Lys has been attracting attention as a variant causing systemic vascular disease. Functional analysis of RNF213 is progressing, and known molecular cascades related to RNF213 expression regulation and cellular activity are gradually being clarified, but the mechanism involved in disease development has not yet been clarified and further analysis is expected.