抗高血压药物标和乳腺癌风险:一个双样本的门德尔随机化研究
Guoqiao Zheng1, Subhayan Chattopadhyay2, Jan Sundquist3,4,5
1Center for Primary Health Care Research, Lund University/Region Skåne, Jan Waldenströms Gata 35, 205 02, Malmö, Sweden. guz@cancer.dk.
European journal of epidemiology
|February 23, 2024
概括
抗高血压药物可能会影响乳腺癌 (BC) 风险. 减少SLC12A2基因表达与BC风险增加有关,而PDE1B基因表达变化影响了雌激素受体阳性BC风险.
科学领域:
- 遗传学 是一个遗传学.
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
背景情况:
- 关于使用抗高血压药物与乳腺癌 (BC) 风险之间的相关性,存在不一致的发现.
- 门德尔随机化 (MR) 提供了一种方法来研究使用遗传变异的潜在因果关系.
研究的目的:
- 调查抗高血压药物对乳腺癌风险的潜在因果作用,使用双样本的门德尔随机化方法.
- 探索抗高血压药物标的基因表达与BC风险之间的关联.
主要方法:
- 使用基因仪器对抗高血压药物标的基因表达进行了双样本孟德尔随机化 (MR).
- 血液中的表达定量特征位点 (eQTL) 被用作基因表达的仪器变量.
- 用全基因组关联研究 (GWAS) 总结统计数据来评估遗传变异与BC风险之间的关联.
- 进行了敏感性分析,包括横向类型评估和局部化.
主要成果:
- 在SLC12A2基因表达和整体BC风险之间发现了显著的关联. 减少SLC12A2表达与增加BC风险相关,特别是对于雌激素受体阳性 (ER+) BC.
- 减少PDE1B基因表达与降低ER+BC的风险有关.
- 对于已识别的关联,没有发现横向质的证据.
结论:
- 抗高血压药物可能介导的SLC12A2和PDE1B基因表达的变化可能会影响乳腺癌风险.
- 减少SLC12A2表达可能会增加BC风险,而PDE1B表达的变化可能会降低ER+BC风险.
更多相关视频
相关概念视频
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
431
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
431
01:17Antihypertensive Drugs: Action of β1 Blockers
447
β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this,...
447
01:25Antihypertensive Drugs: Direct Renin Inhibitors
629
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
629
01:12Hazard Ratio
122
The hazard ratio (HR) is a widely used measure in clinical trials to compare the risk of events, such as death or disease recurrence, between two groups over time. It reflects the ratio of hazard rates—the instantaneous risk of the event occurring—between a treatment group and a control group. This measure provides valuable insights into the relative effectiveness of a treatment by assessing how the risk of an event differs between the two groups.
For example, in a clinical trial...
For example, in a clinical trial...
122
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
731
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
731
01:28Antihypertensive Drugs: Types of β-Blockers
680
β receptors are classified into three subclasses: β1, β2, and β3. β1 receptors are primarily located in the heart and kidneys. When they get activated, they increase heart rate, contractility, and renin release. This process enhances blood pressure and aids in stress management. In contrast, β2 receptors are situated mainly in the lungs, blood vessels, and skeletal muscles. Upon activation, they trigger smooth muscle relaxation, causing bronchodilation and...
680