The role of aquaporin-4 polymorphisms in the development of brain edema after middle cerebral artery occlusion
The role of aquaporin-4 polymorphisms in the development of brain edema after middle cerebral artery occlusion
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DOI：
10.1161/strokeaha.107.500785
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发表时间：
2008-04-01
期刊：
影响因子：
8.3
通讯作者：
Kuhlenbaeumer, Gregor
中科院分区：
文献类型：
--
作者：
Kleffner, Ilka;Bungeroth, May;Kuhlenbaeumer, Gregor
背景和目的——一些患者在大脑中动脉完全闭塞后出现严重的脑水肿，而其他患者则不会。水通道蛋白- 4 (AQP4) 是大脑中的主要水通道，已被证明对于缺血后脑水肿的发展至关重要。我们询问 AQP4 基因的遗传变异是否与大脑中动脉闭塞后脑水肿的严重程度相关。方法 - 我们对 41 名患有或不患有严重脑水肿的大脑中动脉闭塞患者的 AQP4 基因分布的 10 个单核苷酸多态性进行了基因分型，并评估了单一标志物关联以及 AQP4 上的连锁不平衡结构。结果 - 一个单核苷酸多态性（ AQP4 3' 端的 rs9951307）与严重脑水肿相关（显性模型，P = 0.01；OR，0.10；95% CI，保护性 G 等位基因为 0.02 至 0.49）。 AQP4 的连锁不平衡程度较低；无法识别出明确的单倍型块来评估单倍型关联。结论 - 这项探索性研究表明，AQP4 的遗传变异可能导致大脑中动脉闭塞后脑水肿的形成，值得进一步研究。
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.