Association of ACVRL1 Genetic Polymorphisms with Arteriovenous Malformations: A Case-Control Study and Meta-Analysis

To investigate the association between polymorphisms in the gene encoding activin receptorlike kinase 1 (ACVRL1) with brain arteriovenous malformations (BAVMs) using a case-control study in a Chinese Han population, followed by a meta-analysis of the published literature. This study focused on the genotypic analysis of 4 single nucleotide polymorphisms (SNPs; rs2071219, rs706819, rs2293094, and rs11169953) in 50 patients with BAVM and 120 healthy volunteers attending Provincial Hospital in China. A meta-analysis was subsequently conducted involving an extensive literature search for relevant studies. Our cohort study showed a significant association between ACVRL1 rs706819 and increased risk for BAVM. Reduced BAVM risk was correlated with the G allele of rs2293094 and the C allele of rs11169953. However, neither the genotype nor allele frequencies of rs2071219 were found to be significantly different between the BAVM and control groups. Meta-analysis further confirmed that no significant evidence of association was found between rs2071219 and BAVM risk. Haplotype analysis of rs706819, rs2293094, and rs11169953 showed that the GGT haplotype could reduce the risk of BAVM, whereas the GAC haplotype may increase the risk of BAVM. The present study indicates an association between 3 susceptibility SNPs, rs706819, rs2293094, and rs11169953, in the ACVRL1 gene and BAVM. Follow-up functional studies on the ACVRL1 gene are required to better understand its roles in BAVM development.