Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations
BACKGROUND AND PURPOSE: 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.
Medical Subject Headings
Activin Receptors, Type I (genetics); Activin Receptors, Type II; Adult; Antigens, CD; Arteriovenous Malformations (genetics); Brain (pathology); Case-Control Studies; Cohort Studies; Endoglin; Female; Genetic Variation; Genotype; Humans; Male; Middle Aged; Models, Statistical; Odds Ratio; Polymorphism, Genetic; Receptors, Cell Surface; Transforming Growth Factor beta (metabolism); Vascular Cell Adhesion Molecule-1 (genetics)
Digital Object Identifier (DOI)
Pawlikowska, Ludmila; Tran, Mary N.; Achrol, Achal S.; Ha, Connie; Burchard, Esteban; Choudhry, Shweta; Zaroff, Jonathan; Lawton, Michael T.; Castro, Richard; McCulloch, Charles E.; Marchuk, Douglas; Kwok, Pui-Yan; and Young, William L., "Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations" (2005). Neurosurgery. 912.