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Background: Cerebral vasospasm is one of the most serious complications after subarachnoid hemorrhage (SAH). The cerebral artery diameter is regulated by complex physiological mechanisms. Among them the regulation of intracellular calcium homeostasis seems to play a crucial role. Recent data suggest that ryanodine receptors (RYRs) are involved in regulating the luminal calcium concentration in vascular smooth muscle cells. In this gene association investigation, we studied the question as to whether variants in the gene for the ryanodine receptors subtype 1 (RYR1) are associated with symptomatic cerebral vasospasm following SAH., Methods: After informed consent genomic DNA analysis was performed from a whole blood sample in 46 patients suffering from aneurysmal SAH. 16 Patients were affected by symptomatic vasospasm. The RYR1 gene was screened for possible genetic variants by means of direct sequencing. The association of these variants was correlated to the development of symptomatic vasospasm, which was confirmed by clinical examination combined with cerebral angiography, transcranial doppler sonography, or CT scan., Results: Three different genetic RYR1 variants (c.5360C>T, c.6178G>T, and c.7244G>A) were identified in the study. The G/T genotype of RYR1 c.6178G>T was associated with an increased risk for development of symptomatic vasospasm (odds ratio 6.4; 95% CI 1.1-37.8; P = 0.04)., Conclusion: Our pilot study suggests that RYRs are involved in the complex pathophysiology of vasospasm development following SAH. The potential role of RYR1 as a biomarker for prediction of cerebral vasospasm after SAH has to be confirmed in a larger clinical trial.