title: Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations.
abstract: OBJECTIVE
  Mutations in endoglin (ENG) and activin-like kinase (ALK1) cause hereditary hemorrhagic telangiectasias, disorders characterized by pulmonary and brain arteriovenous malformations (BAVMs). We investigated whether polymorphisms in these genes are also associated with sporadic BAVM.
  
  
  METHODS
  A total of 177 sporadic BAVM patients and 129 controls (all subjects white) were genotyped for 2 variants in ALK1 and 7 variants in ENG.
  
  
  RESULTS
  The ALK1 IVS3-35A>G polymorphism was associated with BAVM: (AnyA [AA+AG] genotype: odds ratio, 2.47; 95% CI, 1.38 to 4.44; P=0.002). Two ENG polymorphisms, ENG -1742A>G and ENG 207G>A, showed a trend toward association with BAVM that did not reach statistical significance.
  
  
  CONCLUSIONS
  A common polymorphism in ALK1 is associated with sporadic BAVM, suggesting that genetic variation in genes mutated in familial BAVM syndromes may play a role in sporadic BAVMs.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA 94110, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: Mary N
authors.initials: MN
authors.lastname: Tran
authors.forename: Achal S
authors.initials: AS
authors.lastname: Achrol
authors.forename: Connie
authors.initials: C
authors.lastname: Ha
authors.forename: Esteban
authors.initials: E
authors.lastname: Burchard
authors.forename: Shweta
authors.initials: S
authors.lastname: Choudhry
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zaroff
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lawton
authors.forename: Richard
authors.initials: R
authors.lastname: Castro
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCulloch
authors.forename: Douglas
authors.initials: D
authors.lastname: Marchuk
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: William L
authors.initials: WL
authors.lastname: Young
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D030301:Activin Receptors, Type II; D000328:Adult; D015703:Antigens, CD; D001165:Arteriovenous Malformations / Q000235:genetics*; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D000071063:Endoglin; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; C425364:ACVRL1 protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II