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Biomarker characterization of clinical subtypes of Parkinson Disease
npj Parkinson's Disease ( IF 9.304 ) Pub Date : 2022-08-29 , DOI: 10.1038/s41531-022-00375-y
Xiao Deng 1, 2 , Seyed Ehsan Saffari 3 , Nan Liu 4 , Bin Xiao 1, 2 , John Carson Allen 3 , Samuel Yong Ern Ng 1 , Nicole Chia 1 , Yi Jayne Tan 1 , Xinyi Choi 1 , Dede Liana Heng 1 , Yew-Long Lo 1 , Zheyu Xu 1 , Kay-Yaw Tay 1 , Wing-Lok Au 1, 2 , Adeline Ng 1, 2 , Eng-King Tan 1, 2 , Louis C S Tan 1, 2
Affiliation  

The biological underpinnings of the PD clusters remain unknown as the existing PD clusters lacks biomarker characterization. We try to identify clinical subtypes of Parkinson Disease (PD) in an Asian cohort and characterize them by comparing clinical assessments, genetic status and blood biochemical markers. A total of 206 PD patients were included from a multi-centre Asian cohort. Hierarchical clustering was performed to generate PD subtypes. Clinical and biological characterization of the subtypes were performed by comparing clinical assessments, allelic distributions of Asian related PD gene (SNCA, LRRK2, Park16, ITPKB, SV2C) and blood biochemical markers. Hierarchical clustering method identified three clusters: cluster A (severe subtype in motor, non-motor and cognitive domains), cluster B (intermediate subtype with cognitive impairment and mild non-motor symptoms) and cluster C (mild subtype and young age of onset). The three clusters had significantly different allele frequencies in two SNPs (Park16 rs6679073 A allele carriers in cluster A B C: 67%, 74%, 89%, p = 0.015; SV2C rs246814 T allele distribution: 7%, 12%, 25%, p = 0.026). Serum homocysteine (Hcy) and C-reactive protein (CRP) levels were also significantly different among three clusters (Mean levels of Hcy and CRP among cluster A B C were: 19.4 ± 4.2, 18.4 ± 5.7, 15.6 ± 5.6, adjusted p = 0.005; 2.5 ± 5.0, 1.5 ± 2.4, 0.9 ± 2.1, adjusted p < 0.0001, respectively). Of the 3 subtypes identified amongst early PD patients, the severe subtype was associated with significantly lower frequency of Park16 and SV2C alleles and higher levels of Hcy and CRP. These biomarkers may be useful to stratify PD subtypes and identify more severe subtypes.



中文翻译:

帕金森病临床亚型的生物标志物表征

PD 簇的生物学基础仍然未知,因为现有的 PD 簇缺乏生物标志物表征。我们试图在亚洲队列中识别帕金森病 (PD) 的临床亚型,并通过比较临床评估、遗传状态和血液生化标志物来表征它们。来自多中心亚洲队列的总共 206 名 PD 患者。进行分层聚类以生成 PD 亚型。通过比较临床评估、亚洲相关 PD 基因(SNCA、LRRK2、Park16、ITPKB、SV2C)的等位基因分布和血液生化标志物,对亚型进行临床和生物学表征。分层聚类方法确定了三个聚类:聚类 A(运动、非运动和认知领域的严重亚型),集群 B(具有认知障碍和轻度非运动症状的中间亚型)和集群 C(轻度亚型和年轻发病年龄)。三个簇在两个 SNP 中具有显着不同的等位基因频率(簇 ABC 中的 Park16 rs6679073 A 等位基因携带者:67%、74%、89%、p  = 0.015;SV2C rs246814 T 等位基因分布:7%、12%、25%,p  = 0.026)。三个集群之间的血清同型半胱氨酸 (Hcy) 和 C 反应蛋白 (CRP) 水平也存在显着差异(集群 ABC 中 Hcy 和 CRP 的平均水平为:19.4 ± 4.2, 18.4 ± 5.7, 15.6 ± 5.6,调整后p  = 0.005; 2.5 ± 5.0、1.5 ± 2.4、0.9 ± 2.1,分别调整后的p  < 0.0001)。在早期 PD 患者中发现的 3 种亚型中,严重亚型与 Park16 和 SV2C 等位基因频率显着降低以及 Hcy 和 CRP 水平升高有关。这些生物标志物可能有助于对 PD 亚型进行分层并识别更严重的亚型。

更新日期:2022-08-30
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