{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T18:59:22Z","timestamp":1722884362529},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T00:00:00Z","timestamp":1427932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 NS065705"],"award-info":[{"award-number":["U54 NS065705"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Hereditary hemorrhagic telangiectasia (HHT) is characterized by vascular malformations (VMs) and caused by mutations in TGF\u03b2\/BMP9 pathway genes, most commonly <jats:italic>ENG<\/jats:italic> or <jats:italic>ACVRL1<\/jats:italic>. Patients with HHT have diverse manifestations related to skin and mucosal telangiectases and organ VMs, including arteriovenous malformations (AVM). The clinical heterogeneity of HHT suggests a role for genetic modifiers. We hypothesized that the <jats:italic>ACVRL1<\/jats:italic> c.314\u201335A&gt;G and <jats:italic>ENG<\/jats:italic> c.207G&gt;A polymorphisms, previously associated with sporadic brain AVM, are associated with organ VM in HHT. We genotyped these variants in 716 patients with HHT and evaluated association of genotype with presence of any organ VM, and specifically with brain VM, liver VM and pulmonary AVM, by multivariate logistic regression analyses stratified by HHT mutation. Among all patients with HHT, neither polymorphism was significantly associated with presence of any organ VM; <jats:italic>ACVRL1<\/jats:italic> c.314\u201335A&gt;G showed a trend toward association with pulmonary AVM (OR\u2009=\u20091.48, <jats:italic>P<\/jats:italic>\u2009=\u20090.062). <jats:italic>ACVRL1<\/jats:italic> c.314\u201335A&gt;G was significantly associated with any VM among patients with HHT with <jats:italic>ENG<\/jats:italic> (OR\u2009=\u20092.66, <jats:italic>P<\/jats:italic>\u2009=\u20090.022), but not <jats:italic>ACVRL1<\/jats:italic> (OR\u2009=\u20090.79, <jats:italic>P<\/jats:italic>\u2009=\u20090.52) mutations. <jats:italic>ACVRL1<\/jats:italic> c.314\u201335A&gt;G was also associated with pulmonary AVM and liver VM among <jats:italic>ENG<\/jats:italic> mutation heterozygotes. There were no significant associations between <jats:italic>ENG<\/jats:italic> c.207G&gt;A and any VM phenotype. These results suggest that common polymorphisms in HHT genes other than the mutated gene modulate phenotype severity of HHT disease, specifically presence of organ VM. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36936","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T22:25:58Z","timestamp":1428013558000},"page":"1262-1267","source":"Crossref","is-referenced-by-count":17,"title":["The <i>ACVRL1<\/i> c.314\u201435A&gt;G polymorphism is associated with organ vascular malformations in hereditary hemorrhagic telangiectasia patients with <i>ENG<\/i> mutations, but not in patients with <i>ACVRL1<\/i> mutations"],"prefix":"10.1002","volume":"167","author":[{"given":"Ludmila","family":"Pawlikowska","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Perioperative Care Center for Cerebrovascular Research University of California San Francisco California"},{"name":"Institute for Human Genetics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care Center for Cerebrovascular Research University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana E.","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care Center for Cerebrovascular Research University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E.","family":"McCulloch","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Lawton","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William L.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care Center for Cerebrovascular Research University of California San Francisco California"},{"name":"Department of Neurological Surgery University of California San Francisco California"},{"name":"Department of Neurology University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care Center for Cerebrovascular Research University of California San Francisco California"},{"name":"Institute for Human Genetics University of California San Francisco California"},{"name":"Department of Epidemiology and Biostatistics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie E.","family":"Faughnan","sequence":"additional","affiliation":[{"name":"Division of Respirology Department of Medicine and Li Ka Shing Knowledge Institute St. Michael's Hospital Toronto Canada"},{"name":"Division of Respirology Department of Medicine University of Toronto Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Brain Vascular Malformation Consortium HHT Investigator Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,2]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"5","article-title":"Brain vascular malformation consortium: Overview, progress and future directions","volume":"1","author":"Akers AL","year":"2013","journal-title":"J Rare 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