Klinik für Anästhesiologie & Intensivmedizin, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
Institute for Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen, Germany.
Atherosclerosis. 2020 Oct;310:102-108. doi: 10.1016/j.atherosclerosis.2020.06.020. Epub 2020 Jul 5.
Coronary artery calcification (CAC) is one of the most sensitive and specific markers of coronary atherosclerosis and believed to be heritable. We hypothesized that functionally relevant single-nucleotide polymorphisms (SNPs) in the G-protein signal pathway, which have been previously related to coronary artery disease, are associated with CAC progression.
3108 participants from the Heinz Nixdorf Recall study with CAC measurements at both baseline (CACb) and 5-year follow-up (CAC5y) were included. We genotyped SNPs rs1042714 (ADRB2), rs6026584 and rs12481583 (GNAS), and rs5443 (GNB3) and defined a priori risk alleles derived from literature data. Regression analyses were applied to measures of 5-year CAC progression, unadjusted, adjusted for age, sex, and adjusted for age, sex, log(CACb+1) as well as for cardiovascular risk factors.
The presence of one or more risk alleles was associated with a 26.9% (95% CI 5.5-52.4) increase in 5-year CAC progression (p = 0.011) and a 29.2% (95% CI 5.9-57.6) accelerated increase of CAC over the 5-year period compared to what was expected with respect to the baseline CAC percentile value (p = 0.012). Each of those risk alleles increased the 5-year CAC progression by 4.4% (95% CI 1.3-7.6, p = 0.006) and resulted in a 4.9% accelerated increase of CAC over the 5-year period (95% CI 1.6-8.4, p = 0.004). These unadjusted data did not change after adjustment.
Genetic variations in the G-protein signal pathway are associated with CAC progression in a cumulative fashion, indicating the importance of the pathway for genetic heritability in CAC progression and coronary artery disease.
冠状动脉钙化（CAC）是冠状动脉粥样硬化最敏感和特异的标志物之一，且被认为具有遗传性。我们假设，之前与冠状动脉疾病相关的 G 蛋白信号通路中的功能相关单核苷酸多态性（SNP）与 CAC 进展有关。
本研究纳入了 Heinz Nixdorf 回顾研究中的 3108 名参与者，这些参与者在基线（CACb）和 5 年随访（CAC5y）时均进行了 CAC 测量。我们对 SNP rs1042714（ADRB2）、rs6026584 和 rs12481583（GNAS）以及 rs5443（GNB3）进行了基因分型，并根据文献数据定义了先验风险等位基因。回归分析应用于 5 年 CAC 进展的测量，未经调整、按年龄、性别调整以及按年龄、性别、log（CACb+1）以及心血管危险因素调整。
存在一个或多个风险等位基因与 5 年 CAC 进展增加 26.9%（95%CI 5.5-52.4）相关（p=0.011），与基线 CAC 百分位值相比，5 年内 CAC 加速增加 29.2%（95%CI 5.9-57.6）（p=0.012）。这些风险等位基因中的每一个都使 5 年 CAC 进展增加 4.4%（95%CI 1.3-7.6，p=0.006），并导致 5 年内 CAC 加速增加 4.9%（95%CI 1.6-8.4，p=0.004）。这些未经调整的数据在调整后没有变化。
G 蛋白信号通路中的遗传变异与 CAC 进展呈累积方式相关，表明该通路对 CAC 进展和冠状动脉疾病的遗传易感性很重要。
