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肾素-血管紧张素系统的遗传多态性与帕金森病认知衰退。

Genetic polymorphisms in the renin-angiotensin system and cognitive decline in Parkinson's disease.

机构信息

Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Powstańców Wlkp 72, 70-111, Szczecin, Poland.

Department of Neurological-Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland.

出版信息

Mol Biol Rep. 2021 Jul;48(7):5541-5548. doi: 10.1007/s11033-021-06569-6. Epub 2021 Jul 23.

Abstract

BACKGROUND

Renin-angiotensin system (RAS) influences the central nervous system not only through its peripheral impact-the brain possesses its own local RAS. Studies showed altered RAS components in Parkinson's disease (PD) and their association with oxidative stress which may be linked to neurodegeneration and dementia. Moreover, the protective functions of RAS blockade antagonists against cognitive decline and dementia have been suggested. This study aimed to examine whether genetic variability in RAS genes correlates with cognitive decline in PD.

METHODS AND RESULTS

We genotyped single nucleotide polymorphisms (SNPs) in angiotensinogen (AGT: rs699, rs4762), angiotensin II receptors (AGTR1: rs5186 and AGTR2: rs5194, rs1403543) genes, as well as insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE I/D) gene in 256 PD patients, divided into three groups: without cognitive decline, with mild cognitive impairment and with PD dementia. We did not find any significant differences in the frequencies of the analysed polymorphisms in any of the groups.

CONCLUSIONS

Despite no direct correlation between the investigated polymorphisms in RAS genes and cognitive decline in PD, we believe the impact of those genotypes may be indirect, affecting RAS blockade treatment.

摘要

背景

肾素-血管紧张素系统(RAS)不仅通过其外周影响——大脑拥有自己的局部 RAS 来影响中枢神经系统。研究表明,帕金森病(PD)中 RAS 成分发生改变,且与氧化应激有关,这可能与神经退行性变和痴呆有关。此外,还提出了 RAS 阻断拮抗剂对认知能力下降和痴呆的保护作用。本研究旨在探讨 RAS 基因的遗传变异是否与 PD 患者的认知能力下降相关。

方法和结果

我们对血管紧张素原(AGT:rs699、rs4762)、血管紧张素 II 受体(AGTR1:rs5186、AGTR2:rs5194、rs1403543)基因以及血管紧张素转换酶(ACE I/D)基因中的单核苷酸多态性(SNP)在 256 名 PD 患者中的进行了基因分型,将这些患者分为三组:无认知能力下降组、轻度认知障碍组和 PD 痴呆组。我们没有发现任何组中分析的多态性频率存在显著差异。

结论

尽管 RAS 基因中研究的多态性与 PD 患者的认知能力下降之间没有直接相关性,但我们认为这些基因型的影响可能是间接的,会影响 RAS 阻断治疗。

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