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.
Pawlikowska, L; Tran, MN; Achrol, AS; Ha, C; Burchard, E; Choudhry, S; Zaroff, J; Lawton, MT; Castro, R; McCulloch, CE; Marchuk, D; Kwok, P-Y; Young, WL; UCSF BAVM Study Project,
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