Ballantyne C M, Herd J A, Stein E A, Ferlic L L, Dunn J K, Gotto A M, Marian A J
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
J Am Coll Cardiol. 2000 Nov 1;36(5):1572-8. doi: 10.1016/s0735-1097(00)00918-9.
We sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS).
Apo E genotypes have been associated with plasma lipid levels and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown.
Apo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment.
Subjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4/4 genotype (7.0%, p = 0.02). Subjects with the 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events.
Although subjects with the epsilon4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.
在脂蛋白与冠状动脉粥样硬化研究（LCAS）中，我们试图研究载脂蛋白（apo）E基因分型与基线血浆脂质水平、冠状动脉疾病（CAD）严重程度之间的关联，以及氟伐他汀治疗的反应。
Apo E基因分型与血浆脂质水平和CAD有关。然而，在胆固醇轻度至中度升高的患者中，Apo E基因分型对血浆脂质反应以及CAD进展或消退对他汀类药物治疗的影响尚不清楚。
通过聚合酶链反应和限制性图谱分析确定Apo E基因分型。在320名受试者中，于基线时以及使用氟伐他汀或安慰剂治疗12周后测量血浆脂质。在287名受试者中，于基线时和治疗2.5年后进行定量冠状动脉造影。
与具有3/4或4/4基因型的受试者相比，具有3/3基因型的受试者总胆固醇降低幅度更大（20.4%对15.4%，p = 0.01），低密度脂蛋白（LDL）胆固醇降低幅度更大（28.8%对22.7%，p = 0.03）。相比之下，具有2/3基因型的受试者（n = 10）高密度脂蛋白胆固醇升高幅度（19.1%）大于具有3/3基因型的受试者（4.3%，p = 0.002）以及具有3/4或4/4基因型的受试者（7.0%，p = 0.02）。具有3/4或4/4基因型的受试者既往血管成形术的频率增加，但各基因型之间基线CAD严重程度和基线脂质的其他指标无显著差异，CAD进展或临床事件也无显著差异。
尽管携带ε4等位基因的受试者使用氟伐他汀后LDL胆固醇降低幅度较小，但在CAD进展方面有相似的获益。
