Search for Genetic Variants in the Ryanodine Receptor 1 Gene in Patients with Symptomatic Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

• Published in: Neurocritical care 2011-12, Vol.15 (3), p.410-415
• Main Authors: Rueffert, Henrik, Gumplinger, Anja, Renner, Christof, Dengl, Markus, Reske, Andreas, Kaisers, Udo X., Meixensberger, Jürgen
• Format: Article
• Language: English
• Subjects: Adult; Age; Alleles; Aneurysms; Critical Care Medicine; Female; Gender; Genetic Carrier Screening; Genetic Predisposition to Disease - genetics; Genetic Testing; Genetic Variation - genetics; Genotype; Glasgow Outcome Scale; Hospitals; Humans; Indexing in process; Intensive; Intensive care; Internal Medicine; Male; Medical imaging; Medicine; Medicine & Public Health; Middle Aged; Musculoskeletal system; Mutation; Neurology; Original Article; Patients; Pilot Projects; Polymorphism, Single Nucleotide - genetics; Prognosis; Risk Factors; Ryanodine Receptor Calcium Release Channel - genetics; Smooth muscle; Subarachnoid Hemorrhage - genetics; Variables; Vasospasm, Intracranial - genetics; Veins & arteries
• ISSN: 1541-6933; 1556-0961
• DOI: 10.1007/s12028-011-9542-7

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.