{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:12:09Z","timestamp":1773295929929,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T00:00:00Z","timestamp":1520294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["U54 NS065705"],"award-info":[{"award-number":["U54 NS065705"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2018,5]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Hereditary hemorrhagic telangiectasia (HHT<\/jats:styled-content>) is caused by mutations in TGF<\/jats:styled-content>\u03b2\/BMP<\/jats:styled-content>9 pathway genes and characterized by vascular malformations (VM<\/jats:styled-content>) including arteriovenous malformations (AVM<\/jats:styled-content>) in lung, liver, and brain, which lead to severe complications including intracranial hemorrhage (ICH<\/jats:styled-content>) from brain VM<\/jats:styled-content>. The clinical heterogeneity of HHT<\/jats:styled-content> suggests a role for genetic modifier effects. Common variants in loci that modify phenotype severity in Tgfb<\/jats:italic> knockout mice were previously reported as associated with lung AVM<\/jats:styled-content> in HHT<\/jats:styled-content>. Common variants in candidate genes were reported as associated with sporadic brain AVM<\/jats:styled-content> and\/or ICH<\/jats:styled-content>. We investigated whether these variants are associated with HHT<\/jats:styled-content> organ VM<\/jats:styled-content> or with ICH<\/jats:styled-content> from brain VM<\/jats:styled-content> in 752 Caucasian HHT<\/jats:styled-content> patients enrolled by the Brian Vascular Malformation Consortium.<\/jats:p><\/jats:sec>Methods<\/jats:title>We genotyped 11 candidate variants: four variants reported as associated with lung AVM<\/jats:styled-content> in HHT<\/jats:styled-content> (PTPN<\/jats:styled-content>14<\/jats:italic> rs2936018, USH<\/jats:styled-content>2A<\/jats:italic> rs700024, ADAM<\/jats:styled-content>17<\/jats:italic> rs12474540, rs10495565), and seven variants reported as associated with sporadic BAVM<\/jats:styled-content> or ICH<\/jats:styled-content> (APOE<\/jats:styled-content> \u03b52, ANGPTL<\/jats:styled-content>4<\/jats:italic> rs11672433, EPHB<\/jats:styled-content>4<\/jats:italic> rs314308, IL<\/jats:styled-content>6<\/jats:italic> rs1800795, IL<\/jats:styled-content>1B<\/jats:italic> rs1143627, ITGB<\/jats:styled-content>8<\/jats:italic> rs10486391, TNFA<\/jats:styled-content><\/jats:italic> rs361525). Association of genotype with any VM<\/jats:styled-content>, lung AVM<\/jats:styled-content>, liver VM<\/jats:styled-content>, brain VM<\/jats:styled-content> or brain VM ICH<\/jats:styled-content> was evaluated by multivariate logistic regression adjusted for age, gender, and family clustering.<\/jats:p><\/jats:sec>Results<\/jats:title>None of the 11 variants was significantly associated with any phenotype. There was a trend toward association of USH<\/jats:styled-content>2A<\/jats:italic> rs700024 with ICH<\/jats:styled-content> (OR<\/jats:styled-content>\u00a0=\u00a02.77, 95% CI<\/jats:styled-content>\u00a0=\u00a01.13\u20136.80, p<\/jats:italic>\u00a0=\u00a0.026).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>We did not replicate previously reported associations with HHT<\/jats:styled-content> lung AVM<\/jats:styled-content> and variants in Tgfb<\/jats:italic> modifier loci. We also did not find significant associations between variants reported in sporadic brain AVM<\/jats:styled-content> and VM<\/jats:styled-content> or ICH<\/jats:styled-content> in HHT<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.377","type":"journal-article","created":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T23:52:42Z","timestamp":1520380362000},"page":"350-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Association of common candidate variants with vascular malformations and intracranial hemorrhage in hereditary hemorrhagic telangiectasia"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-9953","authenticated-orcid":false,"given":"Ludmila","family":"Pawlikowska","sequence":"first","affiliation":[{"name":"Center for Cerebrovascular Research Department of Anesthesia and Perioperative Care University of California San Francisco CA USA"},{"name":"Institute for Human Genetics University of California San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Nelson","sequence":"additional","affiliation":[{"name":"Center for Cerebrovascular Research Department of Anesthesia and Perioperative Care University of California San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana E.","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Cerebrovascular Research Department of Anesthesia and Perioperative Care University of California San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E.","family":"McCulloch","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Lawton","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Barrow Neurological Institute Phoenix AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Cerebrovascular Research Department of Anesthesia and Perioperative Care University of California San Francisco CA USA"},{"name":"Institute for Human Genetics University of California San Francisco CA USA"},{"name":"Department of Epidemiology and Biostatistics University of California San Francisco CA USA"}],"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 ON Canada"},{"name":"Division of Respirology Department of Medicine University of Toronto Toronto ON 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":[[2018,3,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000298901.61849.A4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000195133.98378.4b"},{"issue":"1","key":"e_1_2_7_4_1","first-page":"5","article-title":"Brain Vascular Malformation Consortium: Overview, progress and future directions","volume":"1","author":"Akers A. 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