Intermountain Healthcare (Intermountain Medical Center), Murray, UT, USA.
Am J Cardiol. 2013 Sep 15;112(6):799-804. doi: 10.1016/j.amjcard.2013.05.009. Epub 2013 Jun 1.
Lipoprotein(a) (Lp[a]) has gained attention as a heritable coronary artery disease (CAD) risk factor and therapeutic target. Two genetic variants in the LPA gene have been reported to influence Lp(a) levels and increase CAD risk. The aim of this study was to prospectively test these variants for their associations with Lp(a) and CAD risk. Participants (n = 1,400) in the Intermountain Heart Collaborative Study Registry who had Lp(a) cholesterol levels determined at coronary angiography were genotyped for rs3798220 and rs1045587 in LPA. Variants were detected by Taqman polymerase chain reaction. Chi-square and linear and logistic regression tests were used as appropriate among genotypes for Lp(a) and angiographic CAD. Age averaged 63 years; 65% were men; and severe CAD was present in 57%, mild CAD in 12%, and no CAD in 31%. Minor allele frequencies were 0.023 for rs3798220 and 0.090 for rs10455872. In multivariate modeling, only rs10455872 (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.67 to 3.33, p = 1.75 × 10⁻⁹) and rs3798220 (OR 1.99, 95% CI 0.99 to 4.00, p = 0.065) contributed to the prediction of elevated Lp(a) cholesterol. Lp(a) cholesterol was weakly associated with CAD (OR 1.17, 95% CI 1.00 to 1.37, p = 0.055). Rs10455872 strongly predicted prevalent CAD (per allele OR 1.43, 95% CI 1.07 to 1.91, p = 0.0172); the effect size for the rare rs3798220 variant was similar (dominant OR 1.47, 95% CI 0.81 to 2.67, p = 0.20), but power was limited to demonstrate significance. The combined genotype explained only a small percentage (≤4%) of variability in Lp(a) cholesterol and prevalence of angiographic CAD. In conclusion, heritable contributions of LPA rs10455872 and rs3798220 to Lp(a) cholesterol levels and to angiographic CAD were prospectively assessed in this study. The percentage of intersubject variability in Lp(a) cholesterol and the percentage of prevalent CAD explained were small.
脂蛋白(a)（Lp[a]）作为一种遗传性冠心病（CAD）风险因素和治疗靶点受到关注。LPA 基因中的两个遗传变异已被报道可影响 Lp(a)水平并增加 CAD 风险。本研究旨在前瞻性检测这些变异与 Lp(a)和 CAD 风险的相关性。在冠状动脉造影时测定 Lp(a)胆固醇水平的 Intermountain Heart Collaborative 研究注册参与者（n=1400）接受了 LPA 中 rs3798220 和 rs1045587 的基因分型。通过 Taqman 聚合酶链反应检测变体。在基因型之间，适当使用卡方检验、线性和逻辑回归检验来检测 Lp(a)和血管造影 CAD。年龄平均为 63 岁；65%为男性；57%存在严重 CAD，12%存在轻度 CAD，31%无 CAD。rs3798220 的次要等位基因频率为 0.023，rs10455872 的次要等位基因频率为 0.090。在多变量建模中，只有 rs10455872（比值比[OR]2.33，95%置信区间[CI]1.67 至 3.33，p=1.75×10⁻⁹）和 rs3798220（OR 1.99，95%CI 0.99 至 4.00，p=0.065）有助于预测升高的 Lp(a)胆固醇。Lp(a)胆固醇与 CAD 呈弱相关（OR1.17，95%CI1.00 至 1.37，p=0.055）。rs10455872 强烈预测现患 CAD（每等位基因 OR1.43，95%CI1.07 至 1.91，p=0.0172）；罕见 rs3798220 变异的效应大小相似（显性 OR1.47，95%CI0.81 至 2.67，p=0.20），但效力有限，无法证明其显著性。组合基因型仅解释了 Lp(a)胆固醇和血管造影 CAD 患病率变异的一小部分（≤4%）。总之，本研究前瞻性评估了 LPA rs10455872 和 rs3798220 对 Lp(a)胆固醇水平和血管造影 CAD 的遗传贡献。Lp(a)胆固醇和现患 CAD 的个体间变异性百分比解释较小。
