BACKGROUND To examine the association between lipoprotein(a) (Lp(a)) levels, LPA (rs10455872 and rs3798220) and IL1F9 (rs13415097) single nucleotide polymorphisms (SNPs) with coronary artery calcification (CAC), an important predictor for coronary artery disease (CAD). METHODS We used data from 3799 (mean age ± SD: 59.0 ± 7.7 years, 47.1% men) Heinz Nixdorf Recall study participants. We applied linear regression models to explore the relation between the log-transformed Lp(a) levels and LPA and IL1F9 SNPs with loge (CAC + 1). The association between the SNPs and log-transformed Lp(a) levels was further assessed using linear regression. The models were adjusted for age and sex (Model 1) and additionally for Lp(a) levels (Model 2). RESULTS We observed a statistically significant association between log-transformed Lp(a) levels and CAC (Model 1: beta per log-unit increase in Lp(a) levels = 0.11; 95% confidence interval [95% CI] [0.04; 0.18], p = 0.002). Furthermore, the LPA SNP rs10455872 showed a statistically significant association with CAC (Model 1: beta per allele = 0.37 [0.14; 0.61], p = 0.002). The association between rs10455872 and CAC was attenuated after adjustment for Lp(a) levels (Model 2: beta per allele = 0.26 [- 0.01; 0.53], p = 0.06). Both LPA SNPs also showed a statistically significant association with Lp(a) levels (Model 1: betars10455872 per allele: 1.56 [1.46; 1.65], p < 0.0001 and betars3798220 per allele: 1.51 [1.33; 1.69], p < 0.0001)). The Mendelian randomization analysis showed that Lp(a) is a causal risk factor for CAC (estimate per log-unit increase in Lp(a) levels (95% CI), p: 0.27 [0.11; 0.44], p = 0.001). The IL1F9 SNP did not show any statistically significant association with Lp(a) levels or with CAC. CONCLUSIONS We provide evidence for the association of LPA rs10455872 with higher levels of Lp(a) and CAC in our study. The results of our study suggest that rs10455872, mediated by Lp(a) levels, might play a role in promoting the development of atherosclerosis leading to cardiovascular disease events.

中文翻译：

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脂蛋白（a）（Lp（a））水平与Lp（a）基因变异与冠状动脉钙化之间的关联。

背景技术为了检查脂蛋白（a）（Lp（a））水平，LPA（rs10455872和rs3798220）和IL1F9（rs13415097）单核苷酸多态性（SNP）与冠状动脉钙化（CAC）之间的关联，冠状动脉钙化是冠状动脉疾病的重要预测因子（CAD）。方法我们使用了3799名（平均年龄±SD：59.0±7.7岁，男性为47.1％）Heinz Nixdorf Recall研究参与者的数据。我们应用线性回归模型来探讨对数转换的Lp（a）水平与具有loge（CAC +1）的LPA和IL1F9 SNP之间的关系。使用线性回归进一步评估了SNP与对数转化的Lp（a）水平之间的关联。针对年龄和性别（模型1）以及Lp（a）水平（模型2）对模型进行了调整。结果我们观察到对数转换的Lp（a）水平与CAC之间存在统计学上的显着相关性（模型1：Lp（a）水平每log单位增加的beta = 0.11；95％置信区间[95％CI] [0.04; 0.18]，p = 0.002）。此外，LPA SNP rs10455872显示出与CAC有统计学意义的关联（模型1：每个等位基因的beta = 0.37 [0.14; 0.61]，p = 0.002）。调整Lp（a）水平后，rs10455872与CAC之间的关联减弱（模型2：每个等位基因的beta = 0.26 [-0.01; 0.53]，p = 0.06）。两种LPA SNP均也显示出与Lp（a）水平的统计学显着关联（模型1：每个等位基因betars10455872：1.56 [1.46; 1.65]，p <0.0001和每个等位基因betars3798220：1.51 [1.33; 1.69]，p <0.0001） 。孟德尔随机分析显示Lp（a）是CAC的因果风险因素（估计Lp（a）水平每对数单位增加（95％CI），p：0.27 [0.11; 0.44]，p = 0.001）。IL1F9 SNP与Lp（a）水平或CAC均无统计学意义。结论我们为LPA rs10455872与较高水平的Lp（a）和CAC的关联提供了证据。我们的研究结果表明，由Lp（a）水平介导的rs10455872可能在促进导致心血管疾病事件的动脉粥样硬化的发展中发挥作用。