Wittrup H H, Tybjaerg-Hansen A, Abildgaard S, Steffensen R, Schnohr P, Nordestgaard B G
Klinisk biokemisk afdeling, Amtssygehuset i Herlev.
Ugeskr Laeger. 1998 Jun 29;160(27):4067-72.
Lipoprotein lipase degrades triglycerides in plasma and as a by-product produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9214 men and women from a general population sample and 948 patients with ischaemic 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 non-carriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/L), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/L and delta = 0.11 mmol/L, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischaemic heart disease in both genders. On univariate analysis, odds ratios for ischaemic heart disease in probands were 1.89 in women (95% confidence interval: 1.19-3.01) and 0.90 (0.62-1.31) in men, and on multivariate analysis 1.98 (1.11-3.53) in women and 1.02 (0.65-1.60) in men. 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 ischaemic 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 ischaemic 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品。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替代检测。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/L），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/L和0.11 mmol/L）。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%置信区间：1.19 - 3.01），在男性中为0.90（0.62 - 1.31）；多因素分析中，女性为1.98（1.11 - 3.53），男性为1.02（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，不能排除这种替代的男性携带者可能代表了一部分甘油三酯未升高、不易患缺血性心脏病的低高密度脂蛋白个体。
