Variants within the nitric oxide synthase 1 gene are associated with stroke susceptibility
Variants within the nitric oxide synthase 1 gene are associated with stroke susceptibility
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DOI：
10.1016/j.atherosclerosis.2011.11.011
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发表时间：
2012-02-01
期刊：
影响因子：
5.3
通讯作者：
Vicente, Astrid M.
中科院分区：
文献类型：
--
作者：
Manso, Helena;Krug, Tiago;Vicente, Astrid M.
目的：动物研究已经允许重要的见解的作用，一氧化氮合酶（NOS）酶在动脉粥样硬化和高血压，以及在中风。在这项研究中，我们测试的假设，NOS 1和NOS 3基因，分别编码神经元型一氧化氮合酶（nNOS）和内皮型一氧化氮合酶（eNOS），影响中风的易感性和结果后中风events.Methods：我们进行了一项病例对照关联研究，在551例缺血性中风患者和530名对照，以评估NOS 1和NOS 3变异体在中风易感性的作用。在431名患者的亚组中检测了相同基因与卒中结局的相关性。4种NOS 1单核苷酸多态性（SNP）（rs 2293050、rs 2139733、rs7308402和rs 1483757）和四种单倍型在调整人口统计学、临床和生活方式危险因素后与卒中易感性显著相关，并使用错误发现率（FDR）方法校正多次测试（SNP：0.004 <（未校正）P < 0.007和0.036 < FDR q < 0.048;单倍型：0.001 <（未校正）P < 0.010和0.018 < FDR q < 0.032）。NOS 1变异与卒中结局无关。我们没有发现任何证据表明NOS 3基因在中风易感性或outcome.Conclusion中的作用：我们的研究结果突出了NOS 1作为中风的易感因素，但没有证实以前的NOS 3与中风风险的关联研究结果。已知nNOS在动脉粥样硬化发展和血流调节中起主要作用，并且其在中风中的影响可能通过这两个主要临床风险因素介导是合理的。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Animal studies have allowed important insights into the role of the nitric oxide synthase (NOS) enzymes in atherosclerosis and hypertension, as well as in stroke. In this study we tested the hypothesis that the NOS1 and NOS3 genes, respectively encoding neuronal NOS (nNOS) and endothelial NOS (eNOS), influence stroke susceptibility and outcome after a stroke event.Methods: We conducted a case-control association study in 551 ischemic stroke patients and 530 controls to assess the role of NOS1 and NOS3 variants in stroke susceptibility. The same genes were tested for association with stroke outcome in a subset of 431 patients.Results: Four NOS1 single nucleotide polymorphisms (SNPs) (rs2293050, rs2139733, rs7308402 and rs1483757) and four haplotypes were significantly associated with stroke susceptibility after adjusting for demographic, clinical and life-style risk factors, and correcting for multiple testing using the false discovery rate (FDR) method (SNPs: 0.004 < (uncorrected) P < 0.007 and 0.036 < FDR q < 0.048; haplotypes: 0.001 < (uncorrected) P < 0.010 and 0.018 < FDR q < 0.032). NOS1 variants were not associated with stroke outcome. We did not find any evidence for a role of the NOS3 gene in stroke susceptibility or outcome.Conclusion: Our results highlight NOS1 as a susceptibility factor for stroke, but do not corroborate previous NOS3 association findings with stroke risk. nNOS is known to play a major role in atherosclerosis development and in blood flow regulation, and it is plausible that its influence in stroke may be mediated through these two main clinical risk factors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.