ACE variants and risk of intracerebral hemorrhage recurrence in amyloid angiopathy

Abstract

Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (ICH). The aim of the authors was to investigate the influence of clinical characteristics and genetic variants in the ACE, LRP, MMP9, Tafi, VEGFA, CYP11B2, A2M and APOE on ICH recurrence in a cohort of CAA-related ICH patients. Sixty patients were enrolled and new symptomatic ICHs in the 36 mo following the index event were recorded. Leukoaraiosis degree, microbleeds count and variants in the APOE and ACE were associated with ICH recurrence. The rs4311 variant of the ACE was an independent risk factor (p = 0.001), resisting Bonferroni correction. Moreover, carriers of ε2 of the APOE and TT of the rs4311 of the ACE reached 100% recurrence before 18 mo (p < 0.001). Finally, ACE protein level was measured in serum of controls and depended on the rs4311 genotypes, TT carriers presenting higher level than CC carriers (p = 0.012). These results suggest that variants in the ACE are associated with CAA-related ICH recurrence, possibly by modulating ACE protein level.