基于基因组和现实世界数据的口服抗凝剂与痴呆风险的关联评估
Junlong Ma1, Heng Chen2, Chan Zou3
1Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
Progress in neuro-psychopharmacology & biological psychiatry
|December 28, 2023
概括
维生素K对抗剂可能会降低痴呆风险,特别是阿尔茨海默病,而其他口服抗凝剂没有显著的影响. 需要进一步的研究来证实这些发现在临床环境中.
科学领域:
- 药物基因组学 药物基因组学
- 神经退行性疾病的神经退行性疾病
- 药物安全 药物安全
背景情况:
- 观察性研究表明,口服抗凝剂 (OAC) 可能降低老年人的痴呆风险,但证据仍然不确.
- 不同OAC类别和痴呆症亚型之间的关系需要进一步澄清.
研究的目的:
- 调查OAC和痴呆风险之间的因果关系.
- 区分各种OAC类对痴呆症亚型的影响.
主要方法:
- 利用孟德尔的随机化 (MR) 与VKORC1,F2和F10基因的遗传代理.
- 结合MR与药物监测数据和不成比例性分析,以获得可靠的因果推断.
- 评估了与痴呆症,阿尔茨海默病 (AD) 和血管痴呆症 (VaD) 的关联.
主要成果:
- 增加的VKORC1基因表达与更高的痴呆风险有很强的相关性,特别是对于AD (OR=1.28).
- 针对VKORC1的维生素K抗体 (VKAs) 显示出对痴呆的保护作用 (ROR=0.43).
- 对于与痴呆症相关的F2和F10目标基因,没有发现显著的因果关系.
结论:
- 抑制VKORC1或VKA暴露与降低阿尔茨海默氏症痴呆风险有关.
- 有限的证据支持直接口服抗凝剂 (F2和F10抑制剂) 的类似效果.
- 建议对这些发现进行临床验证.
相关概念视频
Dementia
115
Dementia is a collective term for cognitive disorders primarily affecting memory, thinking, and reasoning. It is not a specific disease but a syndrome, with Alzheimer's disease being the most common cause, accounting for approximately 60-80% of cases. Other types include vascular dementia, Lewy body dementia, and frontotemporal dementia. Dementia affects millions worldwide, particularly older adults, though it is not a normal part of aging.
The progression of dementia is generally gradual....
The progression of dementia is generally gradual....
115
Genome-wide Association Studies-GWAS
13.4K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.4K
Genomics
36.4K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
36.4K
Anticoagulant Drugs: Low-Molecular-Weight Heparins
702
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
702
Alzheimer's Disease: Overview
491
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
491
Alzheimer's Disease: Treatment
195
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
195


