Sandholzer C, Boerwinkle E, Saha N, Tong M C, Utermann G
Institute for Medical Biology and Human Genetics, University of Innsbruck, Austria.
J Clin Invest. 1992 Mar;89(3):1040-6. doi: 10.1172/JCI115645.
Elevated lipoprotein(a) (Lp[a]) concentrations are associated with premature coronary heart disease (CHD). In the general population, Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors also affect plasma Lp(a) levels. In addition, Lp(a) has been hypothesized to be an acute phase protein. It is therefore unclear whether the association of Lp(a) concentrations with CHD is primary in nature. We have analyzed apo(a) phenotypes, Lp(a) levels, total cholesterol, and HDL-cholesterol in patients with CHD, and in controls from the general population. Both samples were Chinese individuals residing in Singapore. Lp(a) concentrations were significantly higher in the patients than in the population (mean 20.7 +/- 23.9 mg/dl vs 8.9 +/- 12.9 mg/dl). Apo(a) isoforms associated with high Lp(a) levels (B, S1, S2) were significantly more frequent in the CHD patients than in the population sample (15.9% vs 8.5%, P less than 0.01). Higher Lp(a) concentrations in the patients were in part explained by this difference in apo(a) allele frequencies. Results from stepwise logistic regression analysis indicate that apo(a) type was a significant predictor of CHD, independent of total cholesterol and HDL cholesterol, but not independent of Lp(a) levels. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) levels, and firmly establish the role of Lp(a) as a primary genetic risk factor for CHD.
脂蛋白(a)[Lp(a)]浓度升高与早发性冠心病(CHD)相关。在一般人群中，Lp(a)水平很大程度上由高变载脂蛋白(a)[apo(a)]基因位点的等位基因决定，但其他遗传和环境因素也会影响血浆Lp(a)水平。此外，有人推测Lp(a)是一种急性期蛋白。因此，尚不清楚Lp(a)浓度与CHD的关联本质上是否具有原发性。我们分析了冠心病患者以及来自一般人群的对照者的apo(a)表型、Lp(a)水平、总胆固醇和高密度脂蛋白胆固醇。两个样本均为居住在新加坡的中国人。患者的Lp(a)浓度显著高于一般人群(平均20.7±23.9mg/dl对8.9±12.9mg/dl)。与高Lp(a)水平相关的apo(a)异构体(B、S1、S2)在冠心病患者中比在人群样本中更常见(15.9%对8.5%，P<0.01)。患者中较高的Lp(a)浓度部分可由apo(a)等位基因频率的这种差异来解释。逐步逻辑回归分析结果表明，apo(a)类型是冠心病的一个显著预测因子，独立于总胆固醇和高密度脂蛋白胆固醇，但不独立于Lp(a)水平。数据表明，apo(a)位点的等位基因通过其对Lp(a)水平的影响来决定冠心病风险，并牢固确立了Lp(a)作为冠心病主要遗传风险因素的作用。
