Candidate-gene studies of the atherogenic lipoprotein phenotype: A sib-pair linkage analysis of DZ women twins
Candidate-gene studies of the atherogenic lipoprotein phenotype: A sib-pair linkage analysis of DZ women twins
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DOI：
10.1086/301712
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发表时间：
1998-02-01
影响因子：
9.8
通讯作者：
Humphries, SE
中科院分区：
文献类型：
--
作者：
Austin, MA;Talmud, PJ;Humphries, SE
越来越多的证据支持小而密的LDL和血浆甘油三酯（TG）作为冠心病危险因素的作用，这两种特征都是致动脉粥样硬化脂蛋白表型。虽然家族研究和双胞胎研究已经证明了遗传因素对这些风险因素的影响，但涉及的特定基因仍有待确定。本研究的目的是调查LDL大小、TG和相关致动脉粥样硬化脂蛋白与已知参与脂质代谢的候选基因之间的遗传连锁。连锁分析的基础上的样本126 DZ妇女双胞胎对，避免了潜在的混杂效应的年龄和性别，通过使用一个定量的同胞对连锁分析方法。检测了8个候选基因，包括微粒体TG-转移蛋白（MTP）、肝脂肪酶、脂酶敏感性脂肪酶、载脂蛋白（apo）B、apo CIII、apo E、胰岛素受体和LDL受体的基因：分析表明，apo B基因标记物与LDL大小、血浆TG水平、HDL胆固醇水平和apo B之间存在遗传连锁，所有这些都是致动脉粥样硬化脂蛋白表型的特征。此外，当分析仅限于主要LDL亚类直径>255埃的女性时，保持了连锁的证据，表明载脂蛋白B基因可能影响中等至大尺寸范围内的LDL异质性。此外，在所有女性中，MTP基因与TG之间存在连锁关系。这些发现为遗传因素对致动脉粥样硬化脂蛋白表型的影响及其在动脉粥样硬化遗传易感性中的作用提供了越来越多的证据。
There is a growing body of evidence supporting the roles of small, dense LDL and plasma triglyceride (TG), both features of the atherogenic lipoprotein phenotype, as risk factors for coronary heart disease. Although family studies and twin studies have demonstrated genetic influences on these risk factors, the specific genes involved remain to be determined definitively. The purpose of this study was to investigate genetic linkage between LDL size, TG, and related atherogenic lipoproteins and candidate genes known to be involved in lipid metabolism. The linkage analysis was based on a sample of 126 DZ women twin pairs, which avoids the potentially confounding effects of both age and gender, by use of a quantitative sib-pair linkage-analysis approach. Eight candidate genes were examined, including those for microsomal TG-transfer protein (MTP), hepatic lipase, hormone-sensitive lipase, apolipoprotein (apo) B, apo CIII, apo E, insulin receptor, and LDL receptor: The analysis suggested genetic linkage between markers for the apo B gene and LDL size, plasma levels of TG, of HDL cholesterol, and of apo B, all features of the atherogenic lipoprotein phenotype. Furthermore, evidence for linkage was maintained when the analysis was limited to women with a major LDL-subclass diameter >255 Angstrom, indicating that the apo B gene may influence LDL heterogeneity in the intermediate-to-large size range. In addition, linkage was found between the MTP gene and TG, among all the women. These findings add to the growing evidence for genetic influences on the atherogenic lipoprotein phenotype and its role in genetic susceptibility to atherosclerosis.