Genetic Risk Factors for PD, part 2 (AAN 2004)

Subject: Genetic Risk Factors for PD, part 2 (AAN 2004)

Date: 5/17/2004

E-MOVE reports from the American Academy of Neurology, San Francisco April 25-30, 2004. Page (A), session (S) and poster (P) numbers are from Neurology 2004;62(7), Suppl 5

Glucocerebrosidase mutations as a risk factor for Parkinson’s disease
E Sidransky, O Goker-Alpan, A Lwin, R Schiffmann
S08.001, A88

Mutations in the gene for glucocerebrosidase may contribute to some cases of sporadic PD, according to this report. Glucocerebrosidase mutations cause Gaucher disease, an autosomal recessive glycogen storage disorder.

Dr. Sidransky first described Gaucher disease patients with parkinsonian features but no other neurological involvement. Neuropathology indicated alpha-synuclein glucocerebrosidase-positive inclusions in brain regions associated with both Gaucher disease and diffuse Lewy body disease. Family histories revealed several first-degree relatives with diagnoses of PD.

Analysis of brain bank tissue from 57 patients diagnosed with idiopathic PD revealed heterozygous mutations in the glucocerebrosidase gene in 8 patients, including 5 with the N370S mutation, the most common cause of Gaucher disease. No mutations were found in 43 non-PD controls.

“Should the current findings persist in other cohorts,” Dr. Sidransky said, “mutations in glucocerebrosidase could be a more frequent inherited risk factor than others presently associated with parkinsonism.”

APOE epsilon-2 allele associated with higher prevalence of sporadic Parkinson’s disease
X Huang, PC Chen, C Poole
S08.004, A89-90

Meta-analysis of 22 independent studies indicates that the e2 allele of APOE is a risk factor for PD. The analysis, which included over 2000 patients and 7800 controls, found a 20% increase in risk for PD (relative risk 1.2, 95% confidence interval 1.02-1.42, p<0.04) for those with one e2 allele, versus those with only e3 alleles. No risk or benefit was identified for the e4 allele. Studies of Alzheimer’s disease have consistently indicated a protective effect for e2 in that disease.
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E-MOVE Editor: Richard Robinson, NASW, WE MOVE

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