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Toward A Genetic Test For Parkinson's Disease

  January, 17 2007 4:03
your information resource in human molecular genetics
Molecular markers of early Parkinosn’s disease based on gene expression in blood.
Scherzer, C.R., A.C. Eklund, L.J. Morse, Z. Liao, et al. Proc. Nat. Acad. Sci.,104 (3), 955-960 (January 16, 2007).

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is difficult to diagnose until significant cell loss has already occurred in the substantia nigra, as evidenced by abnormally slow movement and tremor. Even then, other neurological diseases may confound a clinical diagnosis.

The authors of this study provide a first-pass at identifying a set of genetic markers for diagnosing PD. Their work entailed screening venous blood of 31 PD patients and 35 controls, 18 of whom had other neurological diseases such as Alzheimer’s disease and progressive supranuclear palsy. The microarray analysis used more than 22,000 oligonucleotide probes to find differences in RNA content of the blood. Eight unrelated genes that are expressed in the brain were identified, including three implicated in PD: the vitamin D receptor, huntingtin interacting protein 2, and a protein involved in dopamine transporter endocytosis. The other five have not been associated with PD previously.

A test of the biomarker’s accuracy found that there was a significant difference between patients with PD and the normal and disease controls. Those with a score in the highest third had an odds ratio of 5.1 for PD, versus 1.9 for the intermediate third of patients. (The lowest third was used as a reference group with an assigned score of 1.)

The microarray analysis also identified 22 genes whose expression was altered in PD patients, but lacked predictive power since they were found at abnormal levels in other neurodegenerative diseases. Further investigation of these genes seems warranted, as they may shed light on disease pathology. Indeed, one, the heat-shock protein 70-interacting protein ST13 gene may afford an opportunity to follow disease progression.

In all, this study provides enticing leads to follow for the development of a biomarker-based diagnostic test for Parkinson’s disease, as well as an assay for assessing disease progression.

Message posted by: Keith Markey

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