Polymorphism of the prion protein gene in German patients with Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

Introduction: Movement disorders presenting with parkinsonism may share clinical and histopathological features with Creutzfeldt-Jacob disease (CJD). According to Deslys et al. (1994) and Palmer and co-workers (1991) a prion protein (PRNP) genotype homozygous for methionine or valine at codon 129 predisposes to sporadic and iatrogenic CJD.

To investigate a possible genetic link between parkinsonian syndromes and CJD we studied the polymorphism of the PRNP gene at codon 129 in 55 German patients with PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).

Subjects and Methods: Genomic DNA from 35 patients with PD, 11 patients with MSA and 9 patients with PSP was isolated and polymerase chain reaction was used to amplify a 338-base pair fragment of the PRNP gene. Codon 129 polymorphism was studied after digestion of amplicons with MaeII restriction enzyme and further sequencing with an ABI Prism Sequence Analyzer.

For statisical analysis we used SPSS chi2-test and analysis of variances.

Results and Discussion: A total of 27 (49.1%) patients with PD or atypical parkinsonian syndromes were heterozygous for methionine and valine (M/V) at codon 129 of the PRNP gene. Twenty three (41.8%) subjects carried a methionine homozygosity (M/M) and 5 (9.1%) a valine homozygosity (V/V).

The genotype frequencies at codon 129 in the 35 patients with PD were 42.9% (15) M/M, 54.3% (19) M/V and 2.9% (1) V/V, in the MSA group 45.5% (5) M/M, 36.4% (4) M/V and 18.2% (2) V/V, in the PSP patients 33.3% (3) M/M, 44.4% (4) M/V, and 22.2% (2) V/V. In our study, the genotype distribution of patients with PD and atypical parkinsonian syndromes (MSA, PSP) was not significantly different and did not differ from that previously reported for the German population (Lampe et al., 1999). Particularly in PD patients no significant differences were seen between codon 129 heterozygous or homozygous patients with respect to sex, mean age at disease onset or stage of the disease. The majority of patients with tremor dominant PD, however, was heterozygous (80%), whilst methionine homozygosity was rather associated with a hypokinetic-rigid or equivalence type. These results failed to reach statistical significance, though.

In conclusion, in our small group of patients the polymorphism at codon 129 does not seem to contribute to the genetics of PD, MSA or PSP. In addition, a statistically significant influence on the clinical characteristics could not be established.