Associations of Reported Genetic Risk Loci with Sporadic Brain Arteriovenous Malformations: Meta-analysis

An arteriovenous malformation (AVM) is an abnormal nidus of blood vessels that is characterized by a direct connection between arteries and veins without intervening in the capillary network. The exact underlying cause of sporadic AVMs is unknown, but many studies have reported genetic associations between genes that contribute to angiogenesis, vasculogenesis, and inflammation. Eleven studies retrieved from Medline Complete, PubMed, and Google Scholar up to February 2022 were included. Heterogeneity was assessed using I² and Q-tests. Publication bias was also assessed for the shortlisted CDKN2B-AS1 rs1333040 (T > C), ACVRL1 rs2071219 (A > G), and rs11169953 (C > T) polymorphisms. The rs1333040 polymorphism showed a lower association with sporadic brain AVM for T versus C in an allelic model (OR = 0.59, 95% confidence interval [CI] = 0.41-0.84). In the recessive model, rs2071219 for AA + AG vs. GG was OR = 0.62, 95% CI = 0.43-0.9. In the recessive model, rs11169953 CC + CT vs. TT was OR = 0.56, 95% CI = 0.33-0.95. In summary, the results of this study support the association between CDKN2B-AS1 and ACVRL1 polymorphisms and sporadic brain arteriovenous malformations. This study summarized the existing information and showed the need for more replication studies on the genetic basis of sporadic AVM. In the future, more genome-wide studies should be conducted to validate and fill existing gaps in knowledge about the mechanisms of sporadic AVM development.