{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:43:09Z","timestamp":1792014189006,"version":"4.4.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The mechanisms driving the progression of moyamoya disease (MMD) remain unrecognized. There is evidence suggesting that genetic and environmental factors may be associated with intracranial artery stenosis. Here, we aimed to investigate the characteristics of infectious exposure and the association of the\n                      <jats:italic toggle=\"no\">RNF213<\/jats:italic>\n                      (RING finger protein 213) variant and infectious burden (IB) with intracranial artery stenosis of MMD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We prospectively recruited 275 patients with MMD. Participants underwent\n                      <jats:italic toggle=\"no\">RNF213<\/jats:italic>\n                      p.R4810K sequencing. Serum antibody titers of herpes simplex virus, cytomegalovirus, toxoplasma, rubella virus, and Epstein\u2010Barr virus were assessed and combined into an IB score. The degree of intracranial artery stenosis was measured by using the Willis narrowing score (WNS), which was then dichotomized as mild and severe. Multivariate regression analyses were performed to analyze variables associated with severe WNS. Patients with the\n                      <jats:italic toggle=\"no\">RNF213<\/jats:italic>\n                      variant had a higher risk of severe WNS than wild\u2010type individuals (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.003). Patients with MMD with severe WNS showed an increased level of IB score (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001). The\n                      <jats:italic toggle=\"no\">RNF213<\/jats:italic>\n                      variant (odds ratio [OR], 2.832 [95% CI, 1.347\u20135.955];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.006) and IB score (OR, 1.771 [95% CI, 1.286\u20132.439];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001) were significantly associated with severe WNS after adjusting for covariates. Furthermore, the associations between IB score and severe WNS were more prominent among patients with modifiable risk factors of elevated body mass index (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      &lt;0.001), triglycerides (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.011), and homocysteine (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.016).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This study outlined a perspective of the genetic\u2010environmental interactions in the progression of MMD. The\n                      <jats:italic toggle=\"no\">RNF213<\/jats:italic>\n                      variant and increased IB were associated with intracranial artery stenosis in MMD. The study will provide novel insights into the mechanism of disease progression, which may offer opportunities for early intervention of infectious exposure in MMD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.036830","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T07:23:23Z","timestamp":1740986603000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["<i>RNF213<\/i>\n                    Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-0256","authenticated-orcid":false,"given":"Chaofan","family":"Zeng","sequence":"first","affiliation":[{"name":"Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"China National Clinical Research Center for Neurological 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9338-3981","authenticated-orcid":false,"given":"Zihan","family":"Yin","sequence":"additional","affiliation":[{"name":"Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"China National Clinical Research Center for Neurological Diseases","place":["Beijing, China"]},{"name":"Beijing Institute for Brain Disorders","place":["Beijing, China"]},{"name":"Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease","place":["Beijing, China"]},{"name":"Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4879-0729","authenticated-orcid":false,"given":"Junlin","family":"Lu","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University","place":["Chengdu, 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