Polymorphism of the complement 5 gene and cardiovascular outcome in patients with atherosclerosis
Polymorphism of the complement 5 gene and cardiovascular outcome in patients with atherosclerosis
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DOI：
10.1111/j.1365-2362.2012.02669.x
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发表时间：
2012-09-01
影响因子：
5.5
通讯作者：
Mannhalter, Christine
中科院分区：
文献类型：
--
作者：
Hoke, Matthias;Speidl, Walter;Mannhalter, Christine
Eur J Clin Invest 2012; 42（9）：921926摘要背景炎症的体液介质，特别是补体系统，已被描述为在动脉粥样硬化形成中起重要作用。以前，我们发现补体5基因（C5 rs 17611，A>G）的单核苷酸多态性（SNP）与中风独立相关。到目前为止，C5 rs 17611对无症状动脉粥样硬化患者动脉粥样硬化进展和心血管结局的影响尚不清楚。材料与方法我们研究了1065例无症状颈动脉粥样硬化患者的C5 rs 17611。对所有患者分别进行颈动脉粥样硬化进展和首次主要心血管事件（MACE）的前瞻性随访。结果337例患者（31.6%）在中位随访3.0年期间发生了MACE。C5 rs 17611纯合子GG基因型与不良心血管结局显著相关（校正HR：1.36 [95%CI，1.07 - 1.73]; P = 0.01）。按性别分层后，发现C5 rs 17611 CC是男性MACE的独立风险因素（HR 1.50 [95% CI，1.121.83]）。在93例（8.7%）患者中未检测到C5 rs 17611与颈动脉狭窄进展相关。ELISA的性能表明C5 rs 17611变体与C5 a血浆水平显著相关。结论C5 rs 17611 GG基因型与C5 a血浆水平升高相关，并且是男性颈动脉粥样硬化患者不良心血管结局的危险因素。
Eur J Clin Invest 2012; 42 (9): 921926 Abstract Background Humoral mediators of inflammation, in particular the complement system, have been described to play an important role in atherogenesis. Previously, we found a single-nucleotide polymorphism (SNP) in the complement 5 gene (C5 rs17611, A>G) independently associated with stroke. Up to now, the impact of C5 rs17611 on the progression of atherosclerosis and cardiovascular outcome in patients with asymptomatic atherosclerosis was unclear. Materials and Methods We investigated C5 rs17611 in a cohort of 1065 consecutive patients with asymptomatic carotid atherosclerosis. All patients were prospectively followed for the progression of carotid atherosclerosis and the development of a first major cardiovascular event (MACE), respectively. Results Three hundred and thirty-seven patients (31.6%) experienced a MACE during a median follow-up of 3.0 years. The homozygous GG genotype of the C5 rs17611 was significantly associated with adverse cardiovascular outcome (adjusted HR: 1.36 [95% CI, 1.071.73]; P = 0.01). After stratification for sex, C5 rs17611 CC was found to be an independent risk factor for MACE in men (HR 1.50 [95% CI, 1.121.83]). No association of C5 rs17611 with progression of carotid stenosis, observed in 93 (8.7%) patients, was detectable. Performance of ELISA indicated a significant association of the C5 rs17611 variant with C5a plasma levels. Conclusion The C5 rs17611 GG genotype is associated with increased C5a plasma levels and represents a risk factor for adverse cardiovascular outcome in male patients with carotid atherosclerosis.