非洲人群中他汀类药物治疗反应的主要遗传驱动因素和血脂异常的药物遗传学

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-06-01 Epub Date: 2023-11-14 DOI:10.1089/omi.2023.0122
Zizo Lusiki, Dirk Blom, Nyarai D Soko, Smangele Malema, Erika Jones, Brian Rayner, Jonathan Blackburn, Phumla Sinxadi, Michelle T Dandara, Collet Dandara
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引用次数: 0

摘要

“同一个健康”的视角对于解决与人类、非人类动物、植物和生态系统健康有关的地球健康交织在一起的挑战越来越重要。“同一个健康”方针可以使非洲因非传染性、传染性和环境疾病而负担过重的公共卫生系统受益。值得注意的是,2019冠状病毒病大流行揭示了以前被忽视的药物遗传学(PGx)的双重重要性,即针对非传染性疾病和环境病原体进行个性化治疗。例如,血脂异常是一种常见的心脏代谢风险因素,已被确定为独立的COVID-19严重程度风险因素。观察数据表明,COVID-19感染患者接受降脂治疗可能会有更好的结果。然而,在非洲患者中,对这些药物的反应因患者而异,这表明重要药物基因的遗传变异可能起作用。降脂疗法的PGx可能是血脂异常患者以及COVID-19和血脂异常合并症患者治疗反应差异的基础。APOE、ABCB1、CETP、CYP2C9、CYP3A4、CYP3A5、HMGCR、LDLR、NPC1L1和SLCO1B1基因的遗传变异影响他汀类药物的药物基因组学,并且它们单独与血脂异常和COVID-19治疗的差异反应有关。非洲人口在PGx研究中的代表性不足。这导致对其他不同遗传变异的计算不足,而这些变异对于理解血脂异常和COVID-19治疗反应的个体间和群体间差异可能很重要。本专家审查审查并综合了通过非洲“同一个健康”视角看到的突出和优先的PGx变异,以改善血脂异常和COVID-19的个性化医疗并为其提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Major Genetic Drivers of Statin Treatment Response in African Populations and Pharmacogenetics of Dyslipidemia Through a One Health Lens.

A One Health lens is increasingly significant to address the intertwined challenges in planetary health concerned with the health of humans, nonhuman animals, plants, and ecosystems. A One Health approach can benefit the public health systems in Africa that are overburdened by noncommunicable, infectious, and environmental diseases. Notably, the COVID-19 pandemic revealed the previously overlooked two-fold importance of pharmacogenetics (PGx), for individually tailored treatment of noncommunicable diseases and environmental pathogens. For example, dyslipidemia, a common cardiometabolic risk factor, has been identified as an independent COVID-19 severity risk factor. Observational data suggest that patients with COVID-19 infection receiving lipid-lowering therapy may have better outcomes. However, among African patients, the response to these drugs varies from patient to patient, pointing to the possible contribution of genetic variation in important pharmacogenes. The PGx of lipid-lowering therapies may underlie differences in treatment responses observed among dyslipidemia patients as well as patients comorbid with COVID-19 and dyslipidemia. Genetic variations in APOE, ABCB1, CETP, CYP2C9, CYP3A4, CYP3A5, HMGCR, LDLR, NPC1L1, and SLCO1B1 genes affect the pharmacogenomics of statins, and they have individually been linked to differential responses to dyslipidemia and COVID-19 treatment. African populations are underrepresented in PGx research. This leads to poor accounting of additional diverse genetic variants that could be important in understanding interindividual and between-population variations in therapeutic responses to dyslipidemia and COVID-19. This expert review examines and synthesizes the salient and priority PGx variations, as seen through a One Health lens in Africa, to improve and inform personalized medicine in both dyslipidemia and COVID-19.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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