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帕金森病中的人类白细胞抗原多态性与血液生物标志物谱:拉脱维亚队列的一项初步研究

Human Leukocyte Antigen Polymorphism and Blood Biomarker Profiles in Parkinson's Disease: A Pilot Study in a Latvian Cohort.

作者信息

Minibajeva Olga, Karelis Guntis, Zolovs Maksims, Ķēniņa Viktorija

机构信息

Department of Doctoral Studies, Rīga Stradiņš University, LV-1007 Riga, Latvia.

Department of Neurology and Neurosurgery, Riga East University Hospital, LV-1079 Riga, Latvia.

出版信息

Biomedicines. 2024 Nov 27;12(12):2709. doi: 10.3390/biomedicines12122709.

DOI:10.3390/biomedicines12122709
PMID:39767615
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11673695/
Abstract

: Parkinson's disease (PD) is a neurodegenerative disorder characterised by a high prevalence of sporadic cases. Various molecular mechanisms are involved in its pathogenesis. This pilot study aimed to identify potential risk and protective human leukocyte antigen (HLA) alleles in PD, discover candidate alleles for further research, and evaluate potential blood biomarkers. : A total of 43 PD patients and 79 unrelated sex-matched controls were enrolled in this study. We analysed the polymorphism of , , and alleles and the blood levels of biomarkers such as S100 calcium-binding protein A9 (S1000A9), kynurenic acid (KYNA), neurofilament light chain (NfL), and glutamate decarboxylase (GAD1). : We found that the frequencies of the , , and alleles were significantly higher in the PD patients than in the controls, suggesting that these alleles are potential risk factors. Furthermore, the allele was detected more frequently in the PD group when the disease onset was at 60 years or older. On the contrary, the and alleles were less common in the PD patients, indicating a possible protective effect. Regarding biomarkers, the blood levels of S100 calcium-binding protein A9 were significantly higher, and the kynurenic acid levels were significantly lower in the PD group. The NfL levels were also higher in the PD group but did not reach statistical significance, possibly due to the sensitivity limitations of the ELISA method used. The GAD1 levels showed no significant differences between the two groups. : Our findings indicate that the and alleles and the , , and alleles are associated with PD. Moreover, S100 calcium-binding protein A9 and kynurenic acid can be considered potential blood biomarkers for PD. These findings contribute to the growing body of knowledge on PD and offer new directions for further research in Latvian cohorts.

摘要

帕金森病(PD)是一种神经退行性疾病,其散发病例的患病率很高。其发病机制涉及多种分子机制。这项初步研究旨在确定PD中潜在的风险和保护性人类白细胞抗原(HLA)等位基因,发现可供进一步研究的候选等位基因,并评估潜在的血液生物标志物。

本研究共纳入43例PD患者和79名性别匹配的无关对照。我们分析了 、 和 等位基因的多态性以及S100钙结合蛋白A9(S1000A9)、犬尿烯酸(KYNA)、神经丝轻链(NfL)和谷氨酸脱羧酶(GAD1)等生物标志物的血液水平。

我们发现,PD患者中 、 和 等位基因的频率显著高于对照组,表明这些等位基因是潜在的风险因素。此外,当疾病发病年龄在60岁及以上时,PD组中 等位基因的检测频率更高。相反, 和 等位基因在PD患者中较少见,表明可能具有保护作用。关于生物标志物,PD组中S100钙结合蛋白A9的血液水平显著升高,犬尿烯酸水平显著降低。PD组中NfL水平也较高,但未达到统计学意义,可能是由于所用ELISA方法的灵敏度限制。两组之间GAD1水平无显著差异。

我们的研究结果表明, 和 等位基因以及 、 和 等位基因与PD有关。此外,S100钙结合蛋白A9和犬尿烯酸可被视为PD的潜在血液生物标志物。这些发现有助于增加对PD的认识,并为拉脱维亚队列的进一步研究提供新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2f/11673695/bed4fa1c44da/biomedicines-12-02709-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2f/11673695/bed4fa1c44da/biomedicines-12-02709-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2f/11673695/bed4fa1c44da/biomedicines-12-02709-g001.jpg

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本文引用的文献

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Temporal trends in the prevalence of Parkinson's disease from 1980 to 2023: a systematic review and meta-analysis.1980 年至 2023 年帕金森病患病率的时间趋势:系统评价和荟萃分析。
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Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit.GABA 通路在帕金森病运动和非运动症状中的作用:一个双向回路。
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by subtypes.
多民族血统分析阿尔茨海默病和帕金森病的 HLA 基因座揭示了由亚型介导的共同适应性免疫反应。
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The genetic overlap between Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease.阿尔茨海默病、肌萎缩侧索硬化症、路易体痴呆和帕金森病之间的遗传重叠。
Neurobiol Aging. 2023 Jul;127:99-112. doi: 10.1016/j.neurobiolaging.2023.03.004. Epub 2023 Mar 12.
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Molecular Imaging of the GABAergic System in Parkinson's Disease and Atypical Parkinsonisms.帕金森病和非典型帕金森综合征中 GABA 能系统的分子影像学研究。
Curr Neurol Neurosci Rep. 2022 Dec;22(12):867-879. doi: 10.1007/s11910-022-01245-z. Epub 2022 Nov 18.
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Dynamic changes in metabolites of the kynurenine pathway in Alzheimer's disease, Parkinson's disease, and Huntington's disease: A systematic Review and meta-analysis.阿尔茨海默病、帕金森病和亨廷顿病中美氨酸通路代谢物的动态变化:系统评价和荟萃分析。
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