Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts
Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts
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DOI：
10.1038/sj.tpj.6500402
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发表时间：
2007-02-01
影响因子：
2.8
通讯作者：
Rotter, J. I.
中科院分区：
文献类型：
--
作者：
Goodarzi, M. O.;Taylor, K. D.;Rotter, J. I.
脂蛋白脂肪酶 (LPL) 水解循环甘油三酯 (TG)。我们之前表明 LPL 基因中的 3' 端单倍型影响动脉粥样硬化和胰岛素抵抗。这项研究询问了来自冠状动脉搭桥移植后试验的 829 名受试者中这些 LPL 单倍型是否影响对降脂治疗的反应。在基线和洛伐他汀治疗后 4-5 年获得血脂谱。单倍型基于 12 个 SNP。第四个最常见的单倍型 12-4 与治疗后高密度脂蛋白胆固醇 (HDL-C) 增量减少相关。单倍型 12-6、12-7 和 12-8 均与 HDL-C 对治疗的反应增加相关，单倍型 12-2 与 TG 反应降低相关。最常见的单倍型 12-1 可防止移植物恶化或闭塞。单倍型 12-4 降低了 HDL-C 对洛伐他汀的反应，可能与我们之前对该单倍型易患冠状动脉疾病的观察结果一致。 LPL 可能通过对代谢综合征各个方面的多效性影响来影响动脉粥样硬化风险。
Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs). We previously showed that 3'-end haplotypes in the LPL gene influence atherosclerosis and insulin resistance. This study asked whether these LPL haplotypes influence response to lipid-lowering therapy among 829 subjects from the Post-Coronary Artery Bypass Graft trial. Lipid profiles were obtained at baseline and 4-5 years after treatment with lovastatin. Haplotypes were based on 12 SNPs. The fourth most frequent haplotype, 12-4, was associated with a decreased increment in high-density lipoprotein-cholesterol (HDL-C) following treatment. Haplotypes 12-6, 12-7 and 12-8 were each associated with increased HDL-C response to therapy, and haplotype 12-2 with decreased TG response. The most common haplotype, 12-1, was protective against graft worsening or occlusion. Haplotype 12-4 reduced HDL-C response to lovastatin, possibly consistent with our prior observations of this haplotype as predisposing to coronary artery disease. LPL may influence atherosclerosis risk through pleiotropic effects on each aspect of the metabolic syndrome.