Associations of allelic differences at the A-I/C-III/A-IV gene cluster with carotid artery intima-media thickness and plasma lipid transport in hypercholesterolemic-hypertriglyceridemic humans.
Associations of allelic differences at the A-I/C-III/A-IV gene cluster with carotid artery intima-media thickness and plasma lipid transport in hypercholesterolemic-hypertriglyceridemic humans.
复制标题
高胆固醇血症-高甘油三酯血症人类中 A-I/C-III/A-IV 基因簇等位基因差异与颈动脉内膜中层厚度和血浆脂质转运的关联。
DOI：
10.1161/01.atv.14.6.874
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Boerwinkle,E
中科院分区：
文献类型：
--
作者：
Patsch,W;Sharrett,AR;Chen,IY;Lin-Lee,YC;Brown,SA;GottoJr,AM;Boerwinkle,E
血浆胆固醇和甘油三酯水平升高的个体可能比胆固醇或甘油三酯单独升高的个体患冠状动脉疾病的风险更高。A-I/C-III/A-IV基因簇中的序列变异与一些与过早动脉粥样硬化和/或高胆固醇血症相关的疾病的病因学有关，伴有或不伴有胆固醇升高。这导致了这样的假设，即该基因位点的等位基因变异改变了血浆脂质转运并影响动脉粥样硬化的易感性。来自社区动脉粥样硬化风险（ARIC）研究的研究人群包括50名血脂正常的个体，48名血浆胆固醇升高的受试者，47名血浆甘油三酯升高的受试者，和123名血浆胆固醇和甘油三酯均升高的受试者，他们被用来评估Xmn I多态性位点2.5对（kbp）载脂蛋白（apo）A-I结构基因上游、颅外颈动脉内膜-中层增厚和几种血浆脂质因子。在整个研究人群中，8.3-kbp等位基因和6.6-kbp等位基因的相对等位基因频率分别为0.86和0.14，并且在脂质表型之间没有差异。在血浆胆固醇和甘油三酯升高的组中，与8.3-kbp等位基因纯合子相比，6.6-kbp等位基因的受试者颈动脉内膜中层厚度更大（P = 0.034），血浆apoA-I、高密度脂蛋白（HDL）胆固醇和HDL 3胆固醇水平更高（P <0.02）。相比之下，携带6.6 kbp等位基因的受试者血浆载脂蛋白C-II与C-III、C-II与A-IV和E与A-IV的平均比值较低（P <0.05），富含甘油三酯的脂蛋白中载脂蛋白C-II与C-III的平均比值较低（P = 0.026）。因此，编码载脂蛋白A-I、C-III和A-IV的基因中或附近的序列变异可以识别出一组高胆固醇血症-高脂血症患者，他们比其他具有相同脂蛋白表型的人有更高的动脉粥样硬化风险。
Individuals with elevated levels of plasma cholesterol and triglyceride may be at higher risk for coronary artery disease than those with isolated elevations of either cholesterol or triglyceride. Sequence variation in the A-I/C-III/A-IV gene cluster has been implicated in the etiology of some disorders associated with premature atherosclerosis and/or hypertriglyceridemias with or without elevations of cholesterol. This led to the hypothesis that allelic variation at this gene locus alters plasma lipid transport and affects susceptibility for atherosclerosis. The study population, from the Atherosclerosis Risk in Communities (ARIC) Study, consisted of 50 normolipidemic individuals, 48 subjects with elevated plasma cholesterol, 47 subjects with elevated plasma triglyceride, and 123 subjects with both elevated plasma cholesterol and triglyceride who were used to evaluate associations between an Xmn I polymorphic site 2.5 kilobase pairs (kbp) upstream of the structural gene for apolipoprotein (apo) A-I, intimal-medial thickening of the extracranial carotid arteries, and several plasma lipid factors. The relative allele frequencies of the 8.3-kbp allele and the 6.6-kbp allele were .86 and .14, respectively, in the entire study population and did not differ among the lipid phenotypes. In the group with elevated plasma cholesterol and triglyceride, subjects possessing the 6.6-kbp allele exhibited a greater carotid artery intimal-medial thickness (P = .034) and higher plasma levels of apoA-I, high-density lipoprotein (HDL) cholesterol, and HDL3 cholesterol (P < .02) than subjects homozygous for the 8.3-kbp allele. In contrast, subjects with the 6.6-kbp allele displayed lower mean ratios of apolipoproteins C-II to C-III, C-II to A-IV and E to A-IV in plasma (P < .05) and a lower mean ratio of apolipoprotein C-II to C-III in the triglyceride-rich lipoproteins (P = .026). Sequence variation in or near the genes encoding apolipoproteins A-I, C-III, and A-IV may therefore identify a group of hypercholesterolemic-hypertriglyceridemic persons who are at higher risk for atherosclerosis than others with the same lipoprotein phenotype.