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慢性神经障碍:药物治疗监测的遗传和表观遗传标志物。

Chronic Neurological Disorders: Genetic and Epigenetic Markers for Monitoring of Pharmacotherapy.

机构信息

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Neurol India. 2021 Mar-Apr;69(2):252-259. doi: 10.4103/0028-3886.314522.

Abstract

INTRODUCTION

Chronic neurological diseases are a major cause of mortality and morbidity in the world. With increasing life expectancy in the developing world, the incidence and prevalence of these diseases are predicted to rise even further. This has also contributed to an increase in disability-adjusted life years (DALYs) for noncommunicable diseases. Treatment for such diseases also poses a challenge with multiple genetic and epigenetic factors leading to a varied outcome. Personalization of treatment is one way that treatment outcome/prognosis of disease can be improved, and pharmacogenomics plays a significant role in this context.

METHODOLOGY

This article reviewed the evidence pertaining to the association of genetic and epigenetic markers with major neurological disorders like multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD), which are a major source of burden among neurological disorders. Types of studies included are peer-reviewed original research articles from the PubMed database (1999-2018).

RESULTS

This study compiled data regarding specific genetic and epigenetic markers with a significant correlation between the clinical diagnosis of the disease and prognosis of therapy from 65 studies. In a single platform, this review highlights the clues to some vital questions, such as why interferon beta (IFN-β) therapy fails to improve symptoms in all MS patients? why cholinesterase inhibitors fail to improve cognitive impairment in a subset of people suffering from AD? or why some individuals on levodopa (L-DOPA) for PD suffer from side-effects ranging from dyskinesia to hallucination while others do not?

CONCLUSION

This article summarizes the genetic and epigenetic factors that may either require monitoring or help in deciding future pharmacotherapy in a patient suffering from MS, AD, and PD. As the health care system develops and reaches newer heights, we expect more and more of these biomarkers to be used as pharmacotherapeutic outcome indicators.

摘要

简介

慢性神经系统疾病是世界范围内导致死亡率和发病率的主要原因。随着发展中国家预期寿命的延长,这些疾病的发病率和患病率预计将进一步上升。这也导致了与非传染性疾病相关的残疾调整生命年(DALY)的增加。由于多种遗传和表观遗传因素导致治疗结果各不相同,因此此类疾病的治疗也颇具挑战性。治疗结果/疾病预后可以通过治疗个体化来改善,而药物基因组学在这方面发挥着重要作用。

方法

本文回顾了与多发性硬化症(MS)、阿尔茨海默病(AD)和帕金森病(PD)等主要神经系统疾病相关的遗传和表观遗传标志物的证据,这些疾病是神经系统疾病中主要的负担来源。纳入的研究类型是来自 PubMed 数据库的同行评议原始研究文章(1999-2018 年)。

结果

本研究从 65 项研究中汇编了与疾病的临床诊断和治疗预后具有显著相关性的特定遗传和表观遗传标志物的数据。在单个平台上,本综述强调了一些重要问题的线索,例如为什么干扰素-β(IFN-β)治疗不能改善所有 MS 患者的症状?为什么胆碱酯酶抑制剂不能改善一部分 AD 患者的认知障碍?或者为什么一些接受左旋多巴(L-DOPA)治疗 PD 的患者会出现运动障碍、幻觉等副作用,而另一些患者则没有?

结论

本文总结了 MS、AD 和 PD 患者可能需要监测或有助于决定未来药物治疗的遗传和表观遗传因素。随着医疗保健系统的发展和进步,我们预计会有越来越多的这些生物标志物被用作药物治疗的结果指标。

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