Polymorphisms in transforming growth factor-β-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.