β2-Adrenergic Receptor Gene Polymorphisms and Risk of Ischemic Stroke

Background: β2-adrenergic receptors (β2-AR) mediate vasorelaxation in response to adrenergic agents. Genetic polymorphisms of β2-AR were implicated in various cardiovascular and noncardiovascular traits. Methods: We tested the role of the β2AR-16 and β2AR-27 gene variants in the susceptibility to the development of ischemic stroke in a genetically homogenous and clinically well-characterized case-control sample that included 294 cases and 286 controls from Sardinia, Italy. This population was shown to be an optimal study sample for carrying out genetic analyses. Results: Age, hypertension, dyslipidemia, and atrial fibrillation were independent risk factors for stroke in this cohort. We found that the presence of the Glu27 allelic variant was associated with a significantly increased risk of stroke when assuming a recessive mode of inheritance (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.17-2.41; P = .005). The same results were obtained for the subgroup of ischemic strokes of arterial origin (n = 215): OR, 1.71; 95% CI, 1.14-2.57; P = .009. Furthermore, haplotype analysis confirmed that the presence of the Glu27 allele increased the risk of cerebrovascular accidents. Conclusions: Our data suggest that the Glu27 allelic variant of the β2-AR gene may be a determinant of ischemic stroke.