A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease.
A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease.
复制标题
脂蛋白脂肪酶中的常见取代 (Asn291Ser) 与缺血性心脏病风险增加相关。
DOI：
10.1172/jci119323
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
B. Nordestgaard
中科院分区：
文献类型：
--
作者：
H. H. Wittrup;A. Tybjaerg;S. Abildgaard;R. Steffensen;P. Schnohr;B. Nordestgaard
脂蛋白脂肪酶降解血浆中的甘油三酯，并作为副产物产生HDL颗粒。因此，脂蛋白脂酶的遗传变异可能会影响心血管风险。我们测试了来自普通人群样本的9，214名男性和女性以及948名缺血性心脏病患者的脂蛋白脂肪酶中Asn 291 Ser取代。在一般人群中，女性和男性的等位基因频率分别为0.024和0.026。与非携带者相比，女性杂合子先证者的血浆甘油三酯升高（δ = 0.23 mmol/L），而女性和男性携带者的HDL胆固醇降低（分别为δ = 0.18 mmol/L和δ = 0.11 mmol/L）。在6个纯合子携带者中发现了类似的表型。多元Logistic回归分析显示，血浆甘油三酯和高密度脂蛋白胆固醇是男女缺血性心脏病的独立预测因子。单变量分析显示，先证者缺血性心脏病的优势比女性为1.89（95%CI：1.19-3.01），男性为0.90（95%CI：0.62-1.31），多变量分析显示女性为1.98（95%CI：1.11-3.53），男性为1.02（95%CI：0.65-1.60）。这项研究表明，脂蛋白脂肪酶基因中的一个常见突变与血浆甘油三酯升高和HDL胆固醇水平降低有关，因此携带者，特别是女性，似乎易患缺血性心脏病。然而，不能排除这种替代的男性携带者可能代表一个低HDL个体的子集，没有升高的甘油三酯，不容易患缺血性心脏病。
Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9,214 men and women from a general population sample and 948 patients with ischemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/liter), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/liter and delta = 0.11 mmol/liter, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischemic heart disease in both genders. On univariate analysis, odds ratios for ischemic heart disease in probands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0.62-1.31), and on multivariate analysis were 1.98 in women (95% CI: 1.11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides not predisposed to ischemic heart disease.
影响因子：
6.5
作者：
I. Goldberg
通讯作者：
I. Goldberg