纺神星
医学
生物标志物
队列
疾病
内科学
肿瘤科
帕金森病
单倍型
生物信息学
内分泌学
等位基因
基因
遗传学
生物
肾
作者
Milan Zimmermann,Luca P. Köhler,Markéta Kovářová,Stefanie Lerche,Claudia Schulte,Isabel Wurster,Gerrit Machetanz,Christian Deuschle,Ann‐Kathrin Hauser,Thomas Gasser,Daniela Berg,Erwin Schleicher,Walter Maetzler,Kathrin Brockmann
摘要
Abstract Background Parkinson´s disease (PD) has a large phenotypic variability, which may, at least partly, be genetically driven including alterations of gene products. Candidates might not only be proteins associated with disease risk but also pathways that play a role in aging. Objective To evaluate phenotype‐modifying effects of genetic variants in Klotho , a longevity gene. Methods We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL‐VS haplotype in Klotho including a subgroup of 125 PD patients and 50 healthy controls who underwent biochemical cerebrospinal fluid (CSF) analyses of Klotho and fibroblast growth factor 23 as well as vitamin D metabolites. The second cohort comprised 297 patients from the Parkinsonʼs Progression Markers Initiative (PPMI) for validation of genetic−clinical findings. Results PD patients carrying the KL‐VS haplotype demonstrated a shorter interval between PD onset and onset of cognitive impairment (both cohorts) and higher Unified Parkinson´s Disease Rating Scale part III (UPDRS III) scores (PPMI). CSF protein levels of Klotho and fibroblast growth factor 23 were lower in PD patients irrespective of gender compared to controls. Moreover, low CSF levels of Klotho were associated with higher scores in the UPDRS III and Hoehn and Yahr Scale. Conclusions Our results indicate that genetic variants in Klotho together with its corresponding CSF protein profiles are associated with aspects of disease severity in PD. These findings suggest that pathways associated with aging might be targets for future biomarker research in PD.
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