Polymorphisms of VEGFA gene and susceptibility to hemorrhage risk of brain arteriovenous malformations in a Chinese population
Polymorphisms of VEGFA gene and susceptibility to hemorrhage risk of brain arteriovenous malformations in a Chinese population
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中国人群VEGFA基因多态性与脑动静脉畸形出血风险易感性
DOI：
10.1038/aps.2011.76
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发表时间：
2011-08-01
影响因子：
8.2
通讯作者：
Zhao, Yao
中科院分区：
文献类型：
--
作者：
Gong, Zhi-ping;Qiao, Ni-dan;Zhao, Yao
目的：探讨血管内皮生长因子A（VEGFA）基因多态性与脑出血（ICH）的关系。结果：在单位点分析中，rs 1547651与脑出血风险增加相关（与AA基因型相比，调整OR= 2.11，95%CI = 1.01-4.42）。特别是，女性患者中ICH风险增加与该变异相关（校正OR= 3.21，95% CI= 0.99-10.36）。基于单倍型的分析显示，与最常见的单倍型相比，区组1中的单倍型“GC”和区组2中的单倍型“ACC”与BAVM患者ICH风险降低30%-38%相关（分别为P sim= 0.033和P sim= 0.005）。区组2中单倍型“ACC”的保护作用在男性患者和BAVM大小≥ 3 cm的受试者中更明显（校正OR= 0.57，95%CI = 0.34-0.97和校正OR= 0.57，95%CI = 0.31-0.86）。结果提示VEGFA基因变异可能与BAVM的ICH风险有关。前言脑动静脉畸形（BAVM）是脑出血（ICH）的常见原因，尤其是年轻人1。需要准确估计BAVM患者的ICH风险，以帮助指导临床管理。虽然已经确定了与ICH相关的BAVM特征，但仍需要其他稳健和可重复的指标。遗传变异可能影响BAVM的发病机制和临床病程。与临床表现相关的遗传多态性的鉴定将有助于危险分层以及阐明潜在的生物学2。
Aim:To evaluate the influence of the vascular endothelial growth factor A (VEGFA) polymorphisms on risk of presentation with intracerebral hemorrhage (ICH).Methods:Nine selected VEGFA single-nucleotide polymorphisms (SNPs) were genotyped in 311 patients with brain arteriovenous malformations (BAVM) in a Chinese population. Associations between individual SNPs/haplotypes and the hemorrhage risk of BAVMs were evaluated using logistic regression analysis.Results:In the single-locus analysis, rs1547651 was associated with increased risk of ICH (adjusted OR= 2.11, 95% CI= 1.01–4.42 compared with the AA genotype). In particular, an increased risk for ICH was associated with this variant in female patients (adjusted OR= 3.21, and 95% CI= 0.99–10.36). Haplotype-based analyses revealed that haplotype'GC'in block 1 and haplotype'ACC'in block 2 were associated with a 30%–38% reduction in the risk of ICH in patients with BAVMs compared to the most common haplotype (P sim= 0.033 and P sim= 0.005, respectively). The protective effect of haplotype'ACC'in block 2 was more evident in male patients and subjects with BAVMs of a size≥ 3 cm (adjusted OR= 0.57, 95% CI= 0.34–0.97 and adjusted OR= 0.57, 95% CI= 0.31–0.86, respectively).Conclusion:The results suggest that VEGFA gene variants may contribute to ICH risk of BAVM.IntroductionBrain arteriovenous malformations (BAVMs) are a common cause of intracerebral hemorrhage (ICH), especially in young adults 1. An accurate estimate of ICH risk in patients harboring BAVMs is needed to help guide clinical management. Although features of BAVM associated with ICH have been identified, additional robust and reproducible indices are still needed. Genetic variation may influence the pathogenesis and the clinical course of BAVMs. The identification of genetic polymorphisms associated with clinical manifestations would facilitate risk stratification as well as illuminate the underlying biology 2.