Wittrup H H, Tybjaerg-Hansen A, Abildgaard S, Steffensen R, Schnohr P, Nordestgaard B G
Department of Clinical Biochemistry, Herlev University Hospital, Denmark.
J Clin Invest. 1997 Apr 1;99(7):1606-13. doi: 10.1172/JCI119323.
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.
脂蛋白脂肪酶可降解血浆中的甘油三酯，并产生高密度脂蛋白颗粒作为副产物。因此，脂蛋白脂肪酶的基因变异可能会影响心血管疾病风险。我们对来自普通人群样本的9214名男性和女性以及948名缺血性心脏病患者进行了脂蛋白脂肪酶Asn291Ser替换检测。在普通人群中，该等位基因频率在女性和男性中分别为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（差值 = 0.23 mmol/升），而高密度脂蛋白胆固醇在女性和男性携带者中均降低（差值分别为0.18 mmol/升和0.11 mmol/升）。在6名纯合子携带者中也发现了类似的表型。多因素逻辑回归分析显示，血浆甘油三酯和高密度脂蛋白胆固醇是两性缺血性心脏病的独立预测因素。单因素分析中，先证者患缺血性心脏病的比值比在女性中为1.89（95%可信区间：1.19 - 3.01），在男性中为0.90（95%可信区间：0.62 - 1.31）；多因素分析中，女性为1.98（95%可信区间：1.11 - 3.53），男性为1.02（95%可信区间：0.65 - 1.60）。本研究表明，脂蛋白脂肪酶基因中的一个常见单突变与血浆甘油三酯升高和高密度脂蛋白胆固醇水平降低有关，携带者，尤其是女性，似乎易患缺血性心脏病。然而，不能排除这种替换的男性携带者可能是未患缺血性心脏病且甘油三酯未升高的低高密度脂蛋白个体的一个亚组。
