{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:30:32Z","timestamp":1778787032456,"version":"3.51.4"},"reference-count":40,"publisher":"BMJ","issue":"6","funder":[{"name":"Financial Science and Technology Project of Hunan Province, China","award":["422000008"],"award-info":[{"award-number":["422000008"]}]},{"name":"Hunan Province Nature Science Foundation, China","award":["2021JJ30911"],"award-info":[{"award-number":["2021JJ30911"]}]},{"name":"Hunan Province Nature Science Foundation, China","award":["2021JJ31077"],"award-info":[{"award-number":["2021JJ31077"]}]},{"name":"Hunan Province Nature Science Foundation, China","award":["2021JJ31121"],"award-info":[{"award-number":["2021JJ31121"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J NeuroIntervent Surg"],"accepted":{"date-parts":[[2022,4,10]]},"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in bAVM. This study examined genetic variants associated with bAVM through quantitative synthesis and qualitative description of literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five databases were searched to gather potentially relevant articles published up to January 2022. STATA 14.0 software was used for statistical analyses. Pooled odds ratios and 95% confidence intervals were calculated with random effect models, and heterogeneity was assessed using the Cochran Q test and quantified with the I<jats:italic><jats:sup>2<\/jats:sup><\/jats:italic>test. Sensitivity and publication bias were analyzed to test the robustness of the associations. Variants identified in only one study or with great heterogeneity were not suitable for pooling association analysis, and therefore a qualitative systematic review was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 30 papers were included in a systematic review involving 4709 cases and 7832 controls, where 17 papers were in a meta-analysis. A suggested association of bAVM was observed with<jats:italic>ACVRL1<\/jats:italic>rs2071219 in the additive model and<jats:italic>CDKN2B-AS1<\/jats:italic>rs1333040 in the recessive and additive models. Other variants of genes that could not be analyzed were summarized by qualitative description. These genes were mostly involved in bone morphogenic protein\/transforming growth factor beta (BMP\/TGF-\u03b2), vascular endothelial growth factor\/vascular endothelial growth factor receptor (VEGF\/VEGFR), and RAS-mitogen activated protein kinase (MAPK) signaling and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>According to our meta-analysis,<jats:italic>ACVRL1<\/jats:italic>rs2071219 and<jats:italic>CDKN2B-AS1<\/jats:italic>rs1333040 were potentially associated with bAVM. Multiple pathological signaling pathways could affect disease development. Future studies should aim to determine the interaction of candidate genes with environmental risk factors and to elucidate detailed mechanisms of action of variants and genes.<\/jats:p><jats:p>1<\/jats:p><\/jats:sec>","DOI":"10.1136\/neurintsurg-2022-018776","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T11:00:08Z","timestamp":1652439608000},"page":"572-578","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3803-4068","authenticated-orcid":false,"given":"Junyu","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dun","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxia","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"2024052309484277000_15.6.572.1","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1056\/NEJMcp067192","article-title":"Arteriovenous malformations of the brain","volume":"356","author":"Friedlander","year":"2007","journal-title":"N Engl J Med Overseas Ed"},{"key":"2024052309484277000_15.6.572.2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000010968"},{"key":"2024052309484277000_15.6.572.3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000688"},{"key":"2024052309484277000_15.6.572.4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1632"},{"key":"2024052309484277000_15.6.572.5","article-title":"Pediatric brain arteriovenous malformation recurrence: a cohort study, systematic review and meta-analysis","author":"Hak","year":"2021","journal-title":"J Neurointerv Surg"},{"key":"2024052309484277000_15.6.572.6","article-title":"Venous tortuosity as a novel biomarker of rupture risk in arteriovenous malformations: ARI score","volume":"8","author":"Mosteiro","year":"2021","journal-title":"J Neurointerv Surg"},{"key":"2024052309484277000_15.6.572.7","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00001"},{"key":"2024052309484277000_15.6.572.8","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwp350"},{"key":"2024052309484277000_15.6.572.9","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"key":"2024052309484277000_15.6.572.10","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000182253.91167.fa"},{"key":"2024052309484277000_15.6.572.11","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-012-0231-4"},{"key":"2024052309484277000_15.6.572.12","article-title":"Replication study of polymorphisms associated with brain arteriovenous malformation in a population from South of Brazil","volume":"8","author":"Franciscatto","year":"2016","journal-title":"Cureus"},{"key":"2024052309484277000_15.6.572.13","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-312272"},{"key":"2024052309484277000_15.6.572.14","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.wneu.2017.09.047","article-title":"Association of ACVRL1 genetic polymorphisms with arteriovenous malformations: a case-control study and meta-analysis","volume":"108","author":"Ge","year":"2017","journal-title":"World Neurosurg"},{"key":"2024052309484277000_15.6.572.15","doi-asserted-by":"publisher","DOI":"10.1159\/000160215"},{"key":"2024052309484277000_15.6.572.16","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-310094"},{"key":"2024052309484277000_15.6.572.17","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e31822d9881"},{"key":"2024052309484277000_15.6.572.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2010.04.023"},{"key":"2024052309484277000_15.6.572.19","doi-asserted-by":"publisher","DOI":"10.1159\/000322601"},{"key":"2024052309484277000_15.6.572.20","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.10.033","article-title":"Angiopoietin-like proteins 4 (ANGPTL4) gene polymorphisms and risk of brain arteriovenous malformation","volume":"27","author":"Erkinova","year":"2018","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"2024052309484277000_15.6.572.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2010.08.025"},{"key":"2024052309484277000_15.6.572.22","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e31822d9881"},{"key":"2024052309484277000_15.6.572.23","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-012-0202-9"},{"key":"2024052309484277000_15.6.572.24","doi-asserted-by":"publisher","DOI":"10.1159\/000360752"},{"key":"2024052309484277000_15.6.572.25","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-307276"},{"key":"2024052309484277000_15.6.572.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2011.02.010"},{"key":"2024052309484277000_15.6.572.27","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.3171\/2016.6.JNS16665","article-title":"Familial occurrence of brain arteriovenous malformation: a novel ACVRL1 mutation detected by whole exome sequencing","volume":"126","author":"Y\u0131lmaz","year":"2017","journal-title":"J Neurosurg"},{"key":"2024052309484277000_15.6.572.28","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/hgv.2018.1","article-title":"Identification of a rare BMP pathway mutation in a non-syndromic human brain arteriovenous malformation via exome sequencing","volume":"5","author":"Walcott","year":"2018","journal-title":"Hum Genome Var"},{"key":"2024052309484277000_15.6.572.29","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2020.00146","article-title":"High-throughput sequencing to detect novel likely gene-disrupting variants in pathogenesis of sporadic brain arteriovenous malformations","volume":"11","author":"Scimone","year":"2020","journal-title":"Front Genet"},{"key":"2024052309484277000_15.6.572.30","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-105224"},{"key":"2024052309484277000_15.6.572.31","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21124321","article-title":"Germline mutation enrichment in pathways controlling endothelial cell homeostasis in patients with brain arteriovenous malformation: implication for molecular diagnosis","volume":"21","author":"Scimone","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024052309484277000_15.6.572.32","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg-2020-016469"},{"key":"2024052309484277000_15.6.572.33","doi-asserted-by":"crossref","DOI":"10.1016\/j.clineuro.2021.106582","article-title":"RNF213 rare variants and cerebral arteriovenous malformation in a Chinese population","volume":"203","author":"Liu","year":"2021","journal-title":"Clin Neurol Neurosurg"},{"key":"2024052309484277000_15.6.572.34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709449"},{"key":"2024052309484277000_15.6.572.35","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy307"},{"key":"2024052309484277000_15.6.572.36","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0226852","article-title":"Somatic mutations in intracranial arteriovenous malformations","volume":"14","author":"Goss","year":"2019","journal-title":"PLoS One"},{"key":"2024052309484277000_15.6.572.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.04.004"},{"key":"2024052309484277000_15.6.572.38","doi-asserted-by":"crossref","first-page":"e1365","DOI":"10.1016\/j.wneu.2019.03.105","article-title":"KRAS G12D or G12V mutation in human brain arteriovenous malformations","volume":"126","author":"Oka","year":"2019","journal-title":"World Neurosurg"},{"key":"2024052309484277000_15.6.572.39","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3171\/2020.11.JNS202031","article-title":"Somatic mosaicism in the MAPK pathway in sporadic brain arteriovenous malformation and association with phenotype","volume":"136","author":"Gao","year":"2021","journal-title":"J Neurosurg"},{"key":"2024052309484277000_15.6.572.40","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws180"}],"container-title":["Journal of NeuroInterventional Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/neurintsurg-2022-018776","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T16:49:06Z","timestamp":1716482946000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnis.bmj.com\/lookup\/doi\/10.1136\/neurintsurg-2022-018776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,25]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,5,16]]},"published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1136\/neurintsurg-2022-018776"],"URL":"https:\/\/doi.org\/10.1136\/neurintsurg-2022-018776","relation":{},"ISSN":["1759-8478","1759-8486"],"issn-type":[{"value":"1759-8478","type":"print"},{"value":"1759-8486","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,25]]}}}