Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neurosciences, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
Department of Biomedical Genetics and Complex Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3484CX, The Netherlands.
Transl Stroke Res. 2013 Jun;4(3):375-378. doi: 10.1007/s12975-012-0231-4. Epub 2012 Nov 29.
We aimed to replicate the association of the IVS3-35A>G polymorphism in the activin receptor-like kinase (ACVRL) 1 gene and the 207G>A polymorphism in the endoglin (ENG) gene with sporadic brain arteriovenous malformations (BAVM) in Dutch BAVM patients. In addition, we assessed whether these polymorphisms contribute to the risk of BAVM in patients with hereditary haemorrhagic telangiectasia type 1 (HHT1). We genotyped 143 Dutch sporadic BAVM patients and 360 healthy volunteers for four variants in the ACVRL1 gene including IVS3-35A>G and two variants in the ENG gene including 207G>A. Differences in allele and genotype frequencies between sporadic BAVM patients and controls and their combined effect were analysed with a likelihood ratio test. Furthermore, we compared the allele and genotype frequencies between 24 HHT1 patients with a BAVM with those of a relative with HHT1 without a BAVM in a matched pair analysis using Wilcoxon signed rank test. No significant differences in allele frequency were found between sporadic BAVM cases and controls or between HHT1 patients with and without BAVM for any of the polymorphisms or the combination of ACVRL1 and ENG polymorphisms. Meta-analysis of the current and the two previous studies for the ACVRL1 IVS3-35A polymorphism showed a persisting association between the ACVRL1 IVS3-35A polymorphism and risk of sporadic BAVM (odds ratio, 1.86; 95% CI: 1.32-2.61, p<0.001). We did not replicate the previously found association between a polymorphism in ACVRL1 IVS3-35A>G and BAVM in Dutch patients. However, meta-analysis did not rule out a possible effect.
我们旨在复制在荷兰散发性脑动静脉畸形（BAVM）患者中，激活素受体样激酶（ACVRL）1 基因的 IVS3-35A>G 多态性和内皮糖蛋白（ENG）基因的 207G>A 多态性与散发性 BAVM 的关联。此外，我们评估了这些多态性是否会增加遗传性出血性毛细血管扩张症 1 型（HHT1）患者患 BAVM 的风险。我们对 143 名荷兰散发性 BAVM 患者和 360 名健康志愿者进行了 ACVRL1 基因中的四个变体的基因分型，包括 IVS3-35A>G 和 ENG 基因中的两个变体，包括 207G>A。通过似然比检验分析了散发性 BAVM 患者与对照组之间等位基因和基因型频率的差异及其合并效应。此外，我们在配对分析中比较了 24 例 HHT1 患者伴 BAVM 与无 BAVM 的相对 HHT1 患者的等位基因和基因型频率，使用 Wilcoxon 符号秩检验。对于任何多态性或 ACVRL1 和 ENG 多态性的组合，散发性 BAVM 病例与对照组之间或 HHT1 患者伴或不伴 BAVM 之间的等位基因频率均无显著差异。对 ACVRL1 IVS3-35A 多态性的当前和前两项研究的荟萃分析显示，ACVRL1 IVS3-35A 多态性与散发性 BAVM 风险之间存在持续关联（优势比，1.86；95%置信区间：1.32-2.61，p<0.001）。我们没有复制先前在荷兰患者中发现的 ACVRL1 IVS3-35A>G 多态性与 BAVM 之间的关联。然而，荟萃分析并没有排除可能的影响。
