Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations.
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.
Pawlikowska
Ludmila
L
Cardiovascular Research Institute, University of California, San Francisco, CA 94110, USA.
Tran
Mary N
MN
Achrol
Achal S
AS
Ha
Connie
C
Burchard
Esteban
E
Choudhry
Shweta
S
Zaroff
Jonathan
J
Lawton
Michael T
MT
Castro
Richard
R
McCulloch
Charles E
CE
Marchuk
Douglas
D
Kwok
Pui-Yan
PY
Young
William L
WL
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*
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