Abstract T P154: Association of Common Variants in Immune Response Genes with Severity of Familial Cerebral Cavernous Malformation Type 1

Objective: Familial Cerebral Cavernous Malformation type 1 (fCCM1) is an autosomal dominant disease caused by KRIT1 mutations and characterized by brain lesions, which increase in number over time for unknown reasons. Inflammation and altered expression of immune response genes have been observed in human CCM lesions. We investigated whether common variants in immune response genes are associated with fCCM1 disease severity, as manifested by greater lesion burden. Methods: Lesion burden was assessed on susceptibility-weighted MR imaging for 178 fCCM1 subjects, all carriers of the founder common Hispanic mutation (CHM, Q455X in KRIT1) and recruited as part of the Brain Vascular Malformation Consortium study. We selected 321 variants in 12 immune response genes up-regulated in human CCM lesions and represented on the Affymetrix Axiom® Genome-Wide LAT-1 Human Array. Linear regression analyses under an additive model were performed to assess association of genotype with log-lesion burden residuals, after adju...