Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada.
Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada.
Curr Atheroscler Rep. 2022 Jun;24(6):419-426. doi: 10.1007/s11883-022-01018-6. Epub 2022 Apr 7.
Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic hypercholesterolemia have less severe clinical features compared to patients with monogenic familial hypercholesterolemia (FH) caused by rare deleterious variants.
Studies performed in cohorts of patients with both monogenic and polygenic hypercholesterolemia have assessed lipid levels, non-invasive markers of atherosclerosis, and clinical end points, including major adverse cardiovascular events. The totality of data suggests a gradient across genotypes. Specifically, individuals with polygenic hypercholesterolemia have deleterious phenotypes that are intermediate in severity between those in patients with monogenic hypercholesterolemia and in control subjects. Although clinical variables in patients with polygenic hypercholesterolemia are less severe than in those with monogenic hypercholesterolemia, cardiovascular risk is still very high in these patients compared to controls. Patients with polygenic hypercholesterolemia must be treated assertively.
具有小效应的常见 DNA 变异与多基因高胆固醇血症易感性有关。一些临床医生想知道，与由罕见有害变异引起的单基因家族性高胆固醇血症（FH）患者相比，多基因高胆固醇血症患者的临床特征是否不那么严重。
在患有单基因和多基因高胆固醇血症的患者队列中进行的研究评估了血脂水平、动脉粥样硬化的非侵入性标志物以及包括主要不良心血管事件在内的临床终点。所有数据表明存在基因型梯度。具体而言，多基因高胆固醇血症患者的表型具有中间严重程度，介于单基因高胆固醇血症患者和对照者之间。尽管多基因高胆固醇血症患者的临床变量不如单基因高胆固醇血症患者严重，但与对照组相比，这些患者的心血管风险仍然非常高。多基因高胆固醇血症患者必须积极治疗。
