04:06am Wednesday 20 September 2017

Genetic Factors Can Predict the Progression of Parkinson’s Disease

Amsterdam, NL  – Parkinson’s disease is marked by the abnormal accumulation of α-synuclein and the early loss of dopamine neurons in the substantia nigra region of the brain. A polymorphism in the promotor of α-synuclein gene known as NACP-Rep1 has been implicated as a risk factor for the disease.  Now, researchers have found that different variants of NACP-Rep1 and its interaction with the microtubule-associated protein tau (MAPT) H1 haplotype can influence the speed of clinical deterioration in patients with Parkinson’s disease. 

“Our data are the first to show that polymorphisms of NACP and MAPT interact to influence the rate of progression of Parkinson’s disease, a finding with clinical utility,” says lead author Yue Huang, of Neuroscience Research Australia and the University of New South Wales, Sydney, Australia. “Our study shows that genotypes for NACP and MAPT can be used as a surrogate marker for the estimated rate of Parkinson’s disease progression, with positive predictive values of 94-100% for certain genotypes.” 

123 patients with Parkinson’s disease underwent genetic testing to determine NACP-Rep 1 and MAPT H1 allele or genotype.  The patient’s disease severity was measured using the Unified Parkinson’s Disease Rating Scale (UPDRS), and a measurement of disease progression was calculated based on detailed information about disease and symptom onset.

Three common variations, or alleles, of NACP-Rep1 were detected. Patients with one ‘0’ NACP-Rep1 allele had significantly slower disease progression compared to two or no ‘0’ carriers.  This may partially reflect the known protective influence of ‘0’ allele on Parkinson’s disease.  There was a high variation in the estimated rate of disease progression for the ‘0’ allele group due to an interactive effect with the MAPT genotype. The results showed a low relative risk for rapid clinical progression in patients with one NACP-1 ‘0’ allele, or those carrying MAPT non-H1H1 genotype with two NACP-Rep1 ‘0’s.  In contrast there was a high risk of a fast clinical progression in patients carrying MAPT H1H1 genotype with two or no NACP-Rep1 ‘0’s. 

“Based on current knowledge, it is perhaps not surprising that genetic variation predisposing to high a-synuclein expression gives rise to more rapid progression of PD,” notes Dr. Huang. “However, our results suggest that low a-synuclein expression may also be as detrimental in people with high tau expression levels, calling into question the concept that reducing neuronal a-synuclein in all PD patients may be therapeutically advantageous.”

The article is “Interaction between α-Synuclein and Tau Genotypes and the Progression of Parkinson’s Disease,” by Yue Huang, Dominc B. Rowe, and Glenda M. Halliday. Journal of Parkinson’s Disease. 1(2011) 271-276. DOI 10.3233/JPD-2011-11027, published by IOS Press.

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NOTES FOR EDITORS

Full text of the article is available to credentialed journalists.  Contact Daphne Watrin, IOS Press, Tel: +31 20 688 3355, d.watrin@iospress.nl. Journalists wishing to interview the authors should contact Maryke Steffens, Tel: +61-2-9399-1271, m.steffens@neura.edu.au.

ABOUT THE JOURNAL OF PARKINSON’S DISEASE (JPD)

Launched in June 2011 the Journal of Parkinson’s Disease is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis and treatment of Parkinson’s disease. It publishes research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option. www.journalofparkinsonsdisease.com

ABOUT IOS PRESS

Commencing its publishing activities in 1987, IOS Press (www.iospress.nl) serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 130 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.

IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005.

Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008.


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