在接受他类药物的患者中,LPA变体与残留心血管风险有关
Wei-Qi Wei1, Xiaohui Li2, Qiping Feng3
1Department of Biomedical Informatics (W.-Q.W., J.D.M., J.C.D.), Vanderbilt University Medical Center, Nashville, TN.
Circulation
|April 29, 2018
概括
在服用他类药物的患者中,LPA位点的遗传变异与冠心病 (CHD) 事件有关. 这一发现与胆固醇水平无关,表明向脂蛋白 (a) 可能会降低残留风险.
科学领域:
- 遗传学
- 心脏病学
- 药物基因组学
背景情况:
- 冠心病 (CHD) 仍然是全球主要的死亡原因.
- 虽然他类药物可以降低低密度脂蛋白胆固醇 (LDL- C) 和心脏病发病率,但某些患者仍然存在残留风险.
- 在他类药物治疗期间影响这种残留心血管风险的遗传因素基本上是未知的.
研究的目的:
- 鉴定尽管接受了他类药物治疗,但仍发生心血管疾病的患者残留心血管风险的遗传决定因素.
- 调查LPA/PLG位点中的遗传变异与他类药物治疗期间的冠状动脉疾病事件的相关性.
主要方法:
- 在治疗他类药物期间发生心脏病事件的病例和没有事件的对照病例中进行了两阶段的全基因组关联研究 (GWAS).
- 候选变体的复制是在一个独立的队列中进行的.
- 一项全现象关联研究 (PheWAS) 用于探索与最重要的遗传位点相关的其他特征.
主要成果:
- 在分析中,在LPA/ PLG位点发现了7种单核酸多态 (SNPs),在治疗他类药物期间与心脏病事件有显著的关联.
- 最强的关联是内部SNPrs10455872 (P=2.6×10),在一个独立的队列中复制.
- 在LDL-C≤70 mg/ dL的患者中,RS10455872与心脏病事件的关联与他类药物诱导的LDL-C降低是独立的.
结论:
- 在治疗他类药物期间,LPA位点的遗传变异与心脏病事件有关,独立于LDL- C降低.
- 这些发现支持探索针对循环脂蛋白度的治疗策略,以减轻服用他类药物的患者残留心脏病风险.
相关概念视频
01:07Residual Plots
6.5K
A residual plot is a statistical representation of data used to analyze correlation and regression results. It helps verify the requirements for drawing specific conclusions about correlation and regression. To obtain the residual plot, first, the residual for each data value is calculated, which is simply the vertical distance between the observed and the predicted value obtained from the regression equation.
When the residual values are plotted against the variable x, it is called a residual...
When the residual values are plotted against the variable x, it is called a residual...
6.5K
01:26Residual Stresses
658
Residual stresses reside in a structure even after removing the original stress inducer. This phenomenon often arises from varied plastic deformations across different parts of a structure. Consider a rod stretched beyond its yield point. It will not regain its original length due to permanent deformation. Even after load removal, the rod does not entirely lose stress because of uneven plastic deformations, resulting in residual stresses. The computation of these stresses in structures is...
658
02:30Histone Variants at the Centromere
5.1K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
5.1K
01:15Receiver Operating Characteristic Plot
492
A ROC (Receiver Operating Characteristic) plot is a graphical tool used to assess the performance of a binary classification model by illustrating the trade-off between sensitivity (true positive rate) and specificity (false positive rate). By plotting sensitivity against 1 - specificity across various threshold settings, the ROC curve shows how well the model distinguishes between classes, with a curve closer to the top-left corner indicating a more accurate model. The area under the ROC curve...
492
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
1.5K
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.5K
01:12Relative Risk
2.2K
Relative risk (RR) is a statistical measure commonly used in epidemiology to compare the likelihood of a particular event occurring between two groups. This metric is important for evaluating the relationship between exposure to a specific risk factor and the probability of a particular outcome. It plays a crucial role in medical research, public health studies, and risk assessment. Relative risk quantifies how much more (or less) likely an event is to occur in an exposed group compared to an...
2.2K