The role of aquaporin-4 polymorphisms in the development of brain edema after middle cerebral artery occlusion.
OBJECTIVE
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.
Kleffner
Ilka
I
Bungeroth
May
M
Schiffbauer
Hagen
H
Schäbitz
Wolf-Ruediger
WR
Ringelstein
E Bernd
EB
Kuhlenbäumer
Gregor
G
D000368:Aged; D000369:Aged, 80 and over; D051401:Aquaporin 4 / Q000235:genetics*; D001929:Brain Edema / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014057:Tomography, X-Ray Computed
C496030:AQP4 protein, human; D051401:Aquaporin 4