Kronenberg F, König P, Lhotta K, Ofner D, Sandholzer C, Margreiter R, Dosch E, Utermann G, Dieplinger H
Institute of Medical Biology and Human Genetics, Innsbruck, Austria.
Arterioscler Thromb. 1994 Sep;14(9):1399-404. doi: 10.1161/01.atv.14.9.1399.
High lipoprotein(a) [Lp(a)] plasma concentrations are an independent risk factor for atherosclerosis. In the general population, Lp(a) levels are primarily determined by allelic variation at the apolipoprotein(a) [apo(a)] gene locus. Apo(a) isoforms of various sizes are associated with different Lp(a) concentrations. Patients with end-stage renal disease (ESRD) have elevated plasma concentrations of Lp(a), which are not explained by the size variation at the apo(a) gene locus. To further investigate the origin of the elevated Lp(a) plasma concentrations, we examined Lp(a) concentrations and apo(a) phenotypes in 154 ESRD patients undergoing renal transplantation. In a prospective longitudinal study we observed a rapid normalization of Lp(a) levels from an average concentration of 25.9 +/- 28.7 mg/dL before to 17.9 +/- 25.5 mg/dL 3 weeks after renal transplantation (P < .0001). Only patients with high-molecular-weight phenotypes had a significant decrease in Lp(a) plasma concentrations. This study demonstrates the nongenetic origin of elevated Lp(a) concentrations in ESRD patients, which is obviously caused by the disease. It further confirms a phenotype-associated elevation of Lp(a) concentrations in ESRD.
高脂蛋白(a)[Lp(a)]血浆浓度是动脉粥样硬化的独立危险因素。在一般人群中,Lp(a)水平主要由载脂蛋白(a)[apo(a)]基因位点的等位基因变异决定。各种大小的apo(a)异构体与不同的Lp(a)浓度相关。终末期肾病(ESRD)患者的血浆Lp(a)浓度升高,这不能用apo(a)基因位点的大小变异来解释。为了进一步研究血浆Lp(a)浓度升高的原因,我们检测了154例接受肾移植的ESRD患者的Lp(a)浓度和apo(a)表型。在一项前瞻性纵向研究中,我们观察到Lp(a)水平迅速恢复正常,从肾移植前的平均浓度25.9±28.7mg/dL降至肾移植后3周的17.9±25.5mg/dL(P<.0001)。只有高分子量表型的患者血浆Lp(a)浓度有显著下降。这项研究证明了ESRD患者Lp(a)浓度升高的非遗传来源,这显然是由疾病引起的。它进一步证实了ESRD中Lp(a)浓度与表型相关的升高。