Chao Peng, Zhang Xueqin, Zhang Lei, Cui Xinyue, Wang Shanshan, Yang Yining
Department of Cardiology, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China.
Department of Nephropathy, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China.
Front Cardiovasc Med. 2023 Mar 7;10:1041231. doi: 10.3389/fcvm.2023.1041231. eCollection 2023.
Although since the 1980s, the mortality of coronary heart disease(CHD) has obviously decreased due to the rise of coronary intervention, the mortality and disability of CHD were still high in some countries. Etiological studies of acute myocardial infarction(AMI) and CHD were extremely important. In this study, we used two-sample Mendelian randomization(TSMR) method to collect GWAS statistics of osteoprotegerin (OPG), AMI and CHD to reveal the causal relationship between OPG and these two diseases. In total, we identified 7 genetic variants associated with AMI and 7 genetic variants associated with CHD that were not found to be in linkage disequilibrium(LD; < 0.001). Evidence of a positive effect of an OPG genetic susceptibility on AMI was discovered(IVW OR = 0.877; 95% CI = 0.787-0.977; = 0.017; 7 SNPs) and CHD (IVW OR = 0.892; 95% CI = 0.803-0.991; = 0.033; 7 SNPs). After removing the influence of rs1385492, we found that there was a correlation between OPG and AMI/CHD (AMI: weighted median OR = 0.818;95% CI = 0.724-0.950; = 0.001; 6SNPs;CHD: weighted median OR = 0.842; 95% CI = 0.755-0.938; = 1.893 × 10; 6SNPs). The findings of our study indicated that OPG had a tight genetic causation association with MI or CHD. This genetic causal relationship presented us with fresh ideas for the etiology of AMI and CHD, which is an area of research that will continue in the future.
尽管自20世纪80年代以来，由于冠状动脉介入治疗的兴起，冠心病（CHD）的死亡率明显下降，但在一些国家，冠心病的死亡率和致残率仍然很高。急性心肌梗死（AMI）和冠心病的病因学研究极其重要。在本研究中，我们使用两样本孟德尔随机化（TSMR）方法收集骨保护素（OPG）、AMI和CHD的全基因组关联研究（GWAS）统计数据，以揭示OPG与这两种疾病之间的因果关系。我们总共鉴定出7个与AMI相关的基因变异和7个与CHD相关的基因变异，这些变异未发现处于连锁不平衡（LD；<0.001）状态。发现OPG基因易感性对AMI有正向影响的证据（逆方差加权法比值比[IVW OR]=0.877；95%置信区间[CI]=0.787-0.977；P=0.017；7个单核苷酸多态性[SNPs]）以及对CHD有正向影响的证据（IVW OR=0.892；95%CI=0.803-0.991；P=0.033；7个SNPs）。在去除rs1385492的影响后，我们发现OPG与AMI/CHD之间存在相关性（AMI：加权中位数OR=0.818；95%CI=0.724-0.950；P=0.001；6个SNPs；CHD：加权中位数OR=0.842；95%CI=0.755-0.938；P=1.893×10；6个SNPs）。我们的研究结果表明，OPG与心肌梗死或冠心病存在紧密的遗传因果关联。这种遗传因果关系为AMI和CHD的病因学研究提供了新的思路，这是一个未来仍将继续的研究领域。
