Laschkolnig Anja, Kollerits Barbara, Lamina Claudia, Meisinger Christa, Rantner Barbara, Stadler Marietta, Peters Annette, Koenig Wolfgang, Stöckl Andrea, Dähnhardt Doreen, Böger Carsten A, Krämer Bernhard K, Fraedrich Gustav, Strauch Konstantin, Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria.
Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Institute of Epidemiology II, Neuherberg, Germany.
Cardiovasc Res. 2014 Jul 1;103(1):28-36. doi: 10.1093/cvr/cvu107. Epub 2014 Apr 22.
The relevance of lipoprotein(a) [Lp(a)] concentrations and low-molecular-weight (LMW) apo(a) phenotypes in peripheral arterial disease (PAD) has only been investigated by few studies. Therefore, we analysed this association in three independent cohorts and performed a Mendelian Randomization approach using instrumental variable regression.
Lp(a) concentrations, apo(a) phenotypes, and one SNP in the LPA gene (rs10455872) were measured in the CAVASIC study, including 241 male patients with intermittent claudication and 246 age- and diabetes-matched controls as well as in the two population-based studies KORA F3 (n = 3184) and KORA F4 (n = 3080). In KORA F3/F4, 109/80 persons suffered from intermittent claudication, 200/144 from PAD, and 128/103 showed an ankle-brachial index (ABI) <0.9. In CAVASIC, adjusted logistic regression analyses revealed significant associations between an increase of log-Lp(a) per one standard deviation (SD) (OR = 1.28, P = 0.02) as well as LMW apo(a) phenotypes and symptomatic PAD (OR = 1.65, P = 0.03). Linear regression models with continuous ABI showed a significant association in the combined analyses of KORA F3/F4: an increase in log-Lp(a) per one SD (β = -0.006, P = 0.005) and the presence of LMW apo(a) phenotypes (β = -0.011, P = 0.02) or the minor allele of rs10455872 (ß = -0.016, P = 0.03) were associated with a decrease in ABI in the fully adjusted linear and instrumental variable regression models.
Analyses in three independent populations showed significant associations of Lp(a) concentrations, LMW apo(a) phenotypes, and rs10455872 with PAD. This points to a causal relationship between Lp(a) and PAD since the genetically determined apo(a) phenotypes and SNP alleles are indeed associated with PAD.
关于脂蛋白(a)[Lp(a)]浓度及低分子量(LMW)载脂蛋白(a)表型在外周动脉疾病(PAD)中的相关性，仅有少数研究进行过探讨。因此，我们在三个独立队列中分析了这种关联，并采用工具变量回归进行孟德尔随机化分析。
在CAVASIC研究中测量了Lp(a)浓度、载脂蛋白(a)表型以及LPA基因中的一个单核苷酸多态性(SNP)(rs10455872)，该研究包括241例间歇性跛行男性患者和246例年龄及糖尿病情况匹配的对照，同时还在两项基于人群的研究KORA F3(n = 3184)和KORA F4(n = 3080)中进行了测量。在KORA F3/F4中，109/80人患有间歇性跛行，200/144人患有PAD，128/103人的踝臂指数(ABI)<0.9。在CAVASIC中，经校正的逻辑回归分析显示，每增加一个标准差(SD)的log-Lp(a)(比值比[OR]=1.28，P = 0.02)以及LMW载脂蛋白(a)表型与有症状的PAD之间存在显著关联(OR = 1.65，P = 0.03)。采用连续ABI的线性回归模型在KORA F3/F4的联合分析中显示出显著关联：在完全校正的线性和工具变量回归模型中，每增加一个SD的log-Lp(a)(β = -0.006，P = 0.005)、LMW载脂蛋白(a)表型的存在(β = -0.011，P = 0.02)或rs10455872次要等位基因(β = -0.016，P = 0.03)均与ABI降低相关。
在三个独立人群中进行的分析显示，Lp(a)浓度、LMW载脂蛋白(a)表型以及rs10455872与PAD之间存在显著关联。这表明Lp(a)与PAD之间存在因果关系，因为基因决定的载脂蛋白(a)表型和SNP等位基因确实与PAD相关。
