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Genetic factors may help predict progression of Parkinson's disease

Washington, Sat, 17 Dec 2011 ANI
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Washington, Dec 17 (ANI): Different varieties of a-synuclein gene 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, a new study has found.

 

According to Yue Huang and her team from the University of New South Wales, Sydney, Australia, Parkinson's disease is marked by the abnormal accumulation of a-synuclein NACP-Rep1 and the early loss of dopamine neurons in the substantia nigra region of the brain.

 

A polymorphism in the promotor of NACP-Rep1 has been implicated as a risk factor for the 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," Huang said.

 

"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 percent for certain genotypes," she said.

 

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 of the study showed that 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," Huang said.

 

"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," she added. (ANI)

 

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