Introduction: Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin-Angiotensin System (CARAS) study prospectively evaluated associations of common RAS polymorphisms and their relation to aneurysmal subarachnoid hemorrhage (aSAH).
Methods: The CARAS study prospectively enrolled aSAH patients and controls at two academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensin converting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5’exonnuclease (Taqman) genotyping assays and pyrosequencing.
Results: Two hundred and forty eight patients were screened. One hundred and forty nine aSAH patients and 50 controls were available for analysis. There was a dominant effect of allele C of the angiotensin 2 receptor type 2 (AT2) A/C single nucleotide polymorphism (SNP) on aSAH in patients > 55 years of age (OR = 3.48, 95% CI = 1.23–9.84. p = 0.0192) as compared to controls. A recessive effect of allele I of the ACE I/D polymorphism was identified for Hunt & Hess grade in all patients (OR = 2.76, 95% CI 1.17–6.50, p = 0.0206) with subsequent poor functional outcome. There was a similar effect on delayed cerebral ischemia (DCI) in patients = 55 years of age (OR = 3.63, 95% CI 1.04–12.7, p = 0.0439). In patients > 55 years of age, there was a recessive effect of allele A of the AT2 A/C SNP on DCI (OR = 4.70, 95% CI 1.43–15.4, p = 0.0111).
Conclusions: The allele I of the ACE I/D polymorphism was associated with higher Hunt & Hess grade and subsequent poor functional outcome. The ACE I/D polymorphism and the AT2 A/C showed age-dependent associations with aSAH and DCI.
Patient Care: Assessment of genetic variants in patients with cerebral aneurysms may help identify patients at risk for aneurysmal subarachnoid hemorrhage.
Learning Objectives: By the conclusion of this session, participates should be able to describe the role of the renin angiotensin system in aneurysmal subarachnoid hemorrhage.