Polymorphisms in Transforming Growth Factor-β-Related Genes ALK1 and ENG Are Associated With Sporadic Brain Arteriovenous Malformations

Abstract

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.