The Role of Aquaporin-4 Polymorphisms in the Development of Brain Edema After Middle Cerebral Artery Occlusion

• Published in: Stroke (1970) Vol. 39; no. 4; pp. 1333 - 1335
• Main Authors: Kleffner, Ilka, Bungeroth, May, Schiffbauer, Hagen, Schäbitz, Wolf-Ruediger, Ringelstein, E. Bernd, Kuhlenbäumer, Gregor
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.04.2008
• Subjects: Aged; Aged, 80 and over; Aquaporin 4 - genetics; Biological and medical sciences; Brain Edema - diagnostic imaging; Brain Edema - genetics; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Female; Fundamental and applied biological sciences. Psychology; Genotype; Humans; Infarction, Middle Cerebral Artery - diagnostic imaging; Infarction, Middle Cerebral Artery - genetics; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Neurology; Polymorphism, Single Nucleotide; Tomography, X-Ray Computed; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; Cerebral infarction; Stroke; Nervous system diseases; edema; Middle cerebral artery; Cardiovascular disease; brain; polymorphisms; Cerebral disorder; Encephalon; Vascular disease; genetics; Central nervous system disease; Cerebral edema; cerebral infarct; Cerebrovascular disease; middle cerebral artery occlusion; Polymorphism
• ISSN: 0039-2499; 1524-4628; 1524-4628
• DOI: 10.1161/STROKEAHA.107.500785

Background and Purpose— Some patients develop severe brain edema after complete middle cerebral artery occlusion, whereas others do not. Aquaporin-4 ( AQP4 ) is the main water channel in the brain and has been shown to be critical for the development of brain edema after ischemia. We asked whether genetic variation in the AQP4 gene is related to the severity of brain edema after middle cerebral artery occlusion. Methods— We genotyped 10 single nucleotide polymorphisms distributed across the AQP4 gene in 41 patients with middle cerebral artery occlusion with and without severe brain edema and assessed single marker association as well as the linkage dysequilibrium structure across AQP4 . Results— One single nucleotide polymorphism (rs9951307) at the 3′ end of AQP4 was associated with severe brain edema (dominant model, P =0.01; OR, 0.10; 95% CI, 0.02 to 0.49 for the protective G-allele). Linkage dysequilibrium across AQP4 was low; no clear haplotype blocks could be identified for the assessment of haplotype association. Conclusions— This explorative study shows that genetic variation in AQP4 might contribute to brain edema formation after middle cerebral artery occlusion and warrants further investigation.