The signal sequence polymorphism of the MnSOD gene is associated with the degree of carotid atherosclerosis
The signal sequence polymorphism of the MnSOD gene is associated with the degree of carotid atherosclerosis
复制标题
DOI：
10.1016/s0021-9150(03)00091-1
复制
发表时间：
2003-05-01
期刊：
影响因子：
5.3
通讯作者：
Savolainen, MJ
中科院分区：
文献类型：
--
作者：
Kakko, S;Päivänsalo, M;Savolainen, MJ
血管壁细胞的氧化还原状态是动脉粥样硬化的重要决定因素。锰超氧化物歧化酶（MnSOD）是哺乳动物细胞线粒体中的一种重要的抗氧化酶。一个潜在的功能性氨基酸多态性（Ala16Val）已被描述在该酶的信号序列。本研究的目的是检测MnSOD信号序列多态性是否与颈动脉粥样硬化程度相关。对989名中年高血压患者和对照组进行了基因分型。颈动脉粥样硬化通过超声定量为内膜中层厚度（IMT）。信号序列多态性被认为是颈动脉IMT的次要决定因素，解释了1.3%的总体变异，瓦尔等位基因与较高的IMT相关。在女性中，检测到与血浆低密度脂蛋白（LDL）胆固醇水平的显著相互作用，因为LDL胆固醇水平仅在瓦尔等位基因携带者中与颈动脉IMT呈正相关，而瓦尔等位基因仅在血浆LDL胆固醇水平最高的受试者中与较高的IMT相关。总之，MnSOD基因的信号序列多态性是颈动脉IMT的一个次要决定因素，指出氧化还原平衡在动脉粥样硬化形成中的重要性。(C)2003爱思唯尔科学爱尔兰有限公司保留所有权利。
Redox-state of the cells of vascular walls is an important determinant of atherosclerosis. Manganese superoxide dismutase (MnSOD) is an essential anti-oxidant enzyme working in mitochondria of mammalian cells. A potentially functional amino acid polymorphism (Ala16Val) has been described in the signal sequence of the enzyme. The aim of the current study was to test whether the signal sequence polymorphism of the MnSOD would be associated with the degree of carotid atherosclerosis. The polymorphism was genotyped in a sample of 989 middle-aged hypertensive and control subjects. Carotid atherosclerosis was quantified as intima-media thickness (IMT) by ultrasound. The signal sequence polymorphism was found to be a minor determinant of carotid IMT explaining 1.3% of the overall variation, the Val allele associated with the higher IMT. In women, a significant interaction with plasma levels of low-density lipoprotein (LDL) cholesterol was detected, since LDL cholesterol levels were positively correlated with carotid IMT only in the carriers of the Val allele and the Val allele was associated with higher IMT only in the subjects with highest plasma levels of LDL cholesterol. In conclusion, the signal sequence polymorphism of the MnSOD gene is a minor determinant of carotid IMT pointing out the importance of redox-balance in the atherogenesis. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.