Carril Juan C, Cacabelos Ramón
EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine. 15165-Bergondo, Corunna, Spain; Genomic Medicine. Camilo José Cela University 28692-Madrid, Spain.
Curr Genomics. 2017 Oct;18(5):416-429. doi: 10.2174/1389202918666170426165226.
The study of variations in genes involved in the different events that trigger the atherogenic process, such as lipid metabolism (modification of LDL-cholesterol), endothelial function and hypertension, immune response (recruitment of macrophages and foam cell formation) and stability of atherosclerotic plaques (thrombosis), established the risk for suffering a vascular disorder. A total of 2455 cases over 50 years of age were genotyped for a panel of 19 SNPs in 15 genes encoding for proteins involved in the atherogenic process. This study shows the relevance of polymorphisms in APOB (odds ratio (OR), 1.17; 95% confidence interval (95% CI), 0.74-1.85), APOC3 (OR, 1.33; 95% CI, 0.82-2.17) and APOE (OR, 1.75; 95% CI, 1.09-2.80), as genetic risk markers for hypercholesterolemia; polymorphisms in ACE (OR, 1.68; 95% CI, 0.32-8.77) and AGT (OR, 1.74; 95% CI, 0.97-3.14) for hypertension; and in APOE*3/4 (OR, 2.06; 95% CI, 1.70-2.51) and APOE4/*4 (OR, 3.08; 95% CI, 1.85-5.12) as unambiguous markers of dementia.
Our results also showed the transversal importance of proinflammatory cytokines in different stages of atherogenesis, with special relevance of IL6 (OR, 1.39; 95% CI, 0.56-3.49) and TNF (OR, 1.40; 95% CI, 0.92-2.15) related to hypercholesterolemia and hypertension. The set of markers involved in this genetic risk panel makes it a powerful tool in the management of patients with different vascular disorders.
对参与引发动脉粥样硬化过程的不同事件的基因变异进行研究，这些事件包括脂质代谢（低密度脂蛋白胆固醇的修饰）、内皮功能和高血压、免疫反应（巨噬细胞募集和泡沫细胞形成）以及动脉粥样硬化斑块的稳定性（血栓形成），从而确定患血管疾病的风险。对2455名50岁以上的患者进行基因分型，检测15个参与动脉粥样硬化过程的蛋白质编码基因中的19个单核苷酸多态性（SNP）。这项研究表明，载脂蛋白B（优势比（OR），1.17；95%置信区间（95%CI），0.74 - 1.85）、载脂蛋白C3（OR，1.33；95%CI，0.82 - 2.17）和载脂蛋白E（OR，1.75；95%CI，1.09 - 2.80）中的多态性作为高胆固醇血症的遗传风险标志物具有相关性；血管紧张素转换酶（OR，1.68；95%CI，0.32 - 8.77）和血管紧张素原（OR，1.74；95%CI，0.97 - 3.14）中的多态性与高血压相关；而载脂蛋白E*3/4（OR，2.06；95%CI，1.70 - 2.51）和载脂蛋白E4/*4（OR，3.08；95%CI，1.85 - 5.12）作为痴呆的明确标志物。
我们的结果还显示了促炎细胞因子在动脉粥样硬化不同阶段的横向重要性，白细胞介素6（IL6）（OR，1.39；95%CI，0.56 - 3.49）和肿瘤坏死因子（TNF）（OR，1.40；95%CI，0.92 - 2.15）与高胆固醇血症和高血压相关，具有特殊相关性。这个遗传风险 panel 中涉及的一组标志物使其成为管理不同血管疾病患者的有力工具。
