Ryanodine Receptor 1 Polymorphism Is Not Associated with Aneurysmal Subarachnoid Hemorrhage or its Clinical Sequelae

Abstract

OBJECTIVE: The pathophysiologic mechanisms underlying cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remain poorly understand. Ryanodine receptors (RYR) are intracellular calcium channels involved in the regulation of vascular smooth muscle cells and cerebrovascular tone and diameter. Previous work reported an association between an RYR polymorphism and cerebral vasospasm. Here, we sought to assess the impact of that RYR polymorphism on aSAH and its clinical sequelae. METHODS: Blood samples from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The RYR1 single nucleotide polymorphism (SNP) rs35364374 was detected using 5 ' exonuclease (Taqman) genotyping assays. Associations between the RYR1 polymorphism and aSAH and its clinical sequelae were analyzed. RESULTS: Samples from 149 patients with aSAH and 50 controls were available for analysis. Multivariable regression analysis did not show an association of RYR1 SNP rs35364374 with aSAH. Moreover, there was no association of RYR1 SNP rs35364374 with clinical vasospasm, delayed cerebral ischemia, functional outcome at discharge, or functional outcome at last follow-up. CONCLUSIONS: Contrary to a previous report, the RYR1 SNP rs35364374 was not associated with aSAH or its clinical sequelae.