脂蛋白脂肪酶基因突变、血脂水平、冠状动脉粥样硬化的进展/消退、对治疗的反应以及未来临床事件。脂蛋白与冠状动脉粥样硬化研究。

Lipoprotein lipase gene mutations, plasma lipid levels, progression/regression of coronary atherosclerosis, response to therapy, and future clinical events. Lipoproteins and Coronary Atherosclerosis Study.

作者信息

Sing K, Ballantyne C M, Ferlic L, Brugada R, Cushman I, Dunn J K, Herd J A, Pownall H J, Gotto A M, Marian A J

机构信息

Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Atherosclerosis. 1999 Jun;144(2):435-42. doi: 10.1016/s0021-9150(99)00004-0.

DOI:10.1016/s0021-9150(99)00004-0

PMID:10407505

Abstract

Mutations in human lipoprotein lipase (LPL) gene are potential risk factors for susceptibility to coronary artery disease (CAD). The objectives of this study were to determine the influence LPL mutations Asn291Ser and Ser447Ter on plasma lipid levels, regression and progression of CAD, clinical events rate, and response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population. LCAS is a double blind, randomized, placebo-controlled study designed to test the influence of fluvastatin on progression or regression of CAD. The Asn291Ser and Ser447Ter genotypes were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Fasting plasma lipid profiles were measured and quantitative coronary angiography was performed at baseline and 2.5 years following randomization. Fatal and non-fatal cardiovascular events during the follow-up period were recorded. A total of 4% (14/363) and 18% (62/352) of the subjects had the Asn291Ser and Ser447Ter mutations, respectively. Overall, there was no statistically association between the Asn291Ser and Ser447Ter mutations and the baseline or final mean plasma levels of lipids, number of coronary lesions, total occlusions, the mean minimal lumen diameter (MLD) stenoses and the clinical events rate. However, patients with the Ser447Ter variant had a slightly higher baseline high density lipoprotein-cholesterol (HDL-C) level (46.2 +/- 12 vs 43.2 +/- 11, P = 0.057), less increase in plasma HDL levels in response to fluvastatin therapy (3 vs 11%, P = 0.056) and a higher cardiovascular events rate (23 vs 13%, P = 0.056). Thus, the Ser447Ter variant had a modest influence on plasma HDL levels and the rate of cardiovascular events. These changes were of borderline statistical significance. Neither the Ser447Ter nor the Asn291Ser mutation had a major impact on susceptibility to CAD, progression or regression of CAD, clinical events rate or response to fluvastatin therapy in LCAS population.

摘要

人类脂蛋白脂肪酶（LPL）基因突变是冠状动脉疾病（CAD）易感性的潜在危险因素。本研究的目的是确定脂蛋白与冠状动脉粥样硬化研究（LCAS）人群中LPL突变Asn291Ser和Ser447Ter对血脂水平、CAD的消退和进展、临床事件发生率以及氟伐他汀治疗反应的影响。LCAS是一项双盲、随机、安慰剂对照研究，旨在测试氟伐他汀对CAD进展或消退的影响。通过聚合酶链反应（PCR）和限制性酶切确定Asn291Ser和Ser447Ter基因型。在基线和随机分组后2.5年测量空腹血脂谱并进行定量冠状动脉造影。记录随访期间的致命和非致命心血管事件。分别有4%（14/363）和18%（62/352）的受试者有Asn291Ser和Ser447Ter突变。总体而言，Asn291Ser和Ser447Ter突变与脂质的基线或最终平均血浆水平、冠状动脉病变数量、完全闭塞、平均最小管腔直径（MLD）狭窄以及临床事件发生率之间无统计学关联。然而，携带Ser447Ter变异的患者基线高密度脂蛋白胆固醇（HDL-C）水平略高（46.2±12 vs 43.2±11，P = 0.057），对氟伐他汀治疗的血浆HDL水平升高较少（3% vs 11%，P = 0.056），心血管事件发生率较高（23% vs 13%，P = 0.056）。因此，Ser447Ter变异对血浆HDL水平和心血管事件发生率有适度影响。这些变化具有边缘统计学意义。在LCAS人群中，Ser447Ter和Asn291Ser突变对CAD易感性、CAD进展或消退、临床事件发生率或氟伐他汀治疗反应均无重大影响。