Genetic Risk Factors in PD, part 1 (AAN 2004)

Subject: Genetic Risk Factors in PD, part 1 (AAN 2004)

Date: 5/15/2004

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

1. Glutathione S-transferase allelic variant modifies the onset age of Parkinson’s disease caused by the A53T alpha-synuclein mutation
LI Golbe, G DiIorio, KM Markopoulou, A Athanassiadou, S Papapetropoulos, RL Watts, JM Vance, V Bonifati, TA Williams, JR Spychala, ES Stenroos, WG Johnson
S18.003, A176

Less biochemically active allelic variants of glutathione S-transferase lower the age of onset in autosomal dominant PD, according to this study.

Genotyping for GST allelic variants was performed on 36 members of Italian and Greek families with PD due to the A53T mutation in alpha-synuclein. As a group, the mean age of onset was 45.2 years. For the P1 isoenzyme, age of onset was affected by the A313G substitution. Patients with the G/G genotype had a mean age at onset at 31 years, versus A/G or A/A patients with mean onset of 46.5 years. For the Z1 isoenzyme, age of onset was affected by the A94G substitution. Patients with the A/A form had a mean age of onset of 40 years, versus A/G or G/G patients with mean onset at 46 years. In each case, the mutation associated with lower age of onset is the biochemically less active form.

According to the authors, these results suggest that these GST isoenzymes “detoxify one or more agents that accelerate neuronal loss in at least the form of PD caused by this PARK1 mutation.” A previous study implicating GST variants in PD risk in pesticide users is archived at http://www.mdvu.org/emove/article.asp?ID=26

2. Alpha-synuclein gene duplication is responsible for familial Parkinson’s disease
P Ibanez, AM Bonnet, B Debarges, E Lohmann, F Tison, P Pollak, Y Agid, A Durr, A Brice
P01.004, A25

Genetic analysis of 119 patients with autosomal dominant PD revealed 2 with duplications in the alpha-synuclein gene. The authors report the phenotype of these patients was indistinguishable from idiopathic PD, in contrast to recently reported patients with gene triplication (http://www.mdvu.org/emove/article.asp?ID=634)
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E-MOVE Editor: Richard Robinson, NASW, WE MOVE

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