Letters to the Editor

The thermolabile variant of 5,10-meth-ylenetetrahydrofolate reductase is not associated with Parkinson's disease Oxidative damage has been suggested as a potential mechanism for both atherosclerosis and neurodegenerative disorders such as Parkinson's disease.' One report has noted a 2-5-fold increased risk of cardiovascular disease among patients with Parkinson's disease ,2 suggesting that a common genetic variant may contribute to both diseases. One such candidate genetic factor, the ApoE-E4 allele, is found at a raised frequency in those with cardiovascular disease and Alzheimer's disease, but was recently shown not to be raised in patients with Parkinson's disease.3 Homocysteine is a pro-oxidant that acts via the copper catalysed, oxygen dependent, production of hydrogen peroxide. Moderately raised concentrations of the amino acid homocysteine (mild hyperhomocysteinae-mia) confer a twofold to threefold risk of vascular disease. In a significant proportion of cases mild hyperhomocysteinaemia arises from the interaction of the homozygous thermolabile (tt) genotype of 5,10-methyl-enetetrahydrofolate reductase (MTHFR) with suboptimal folate and B12 nutrition.4 The tt genotype has also been directly associated with cardiovascular disease.5 We therefore determined the prevalence of the tt genotype in patients with Parkinson's disease. Patients with early onset Parkinson's disease (n = 188) and matched controls (n = 184) were selected as described previously .3 Cases had initial symptoms before the age of 56 years, and were bom after 1924. Controls were age and frequency matched by five-year bands, sex, and urban-rural indicator. Genotyping for the tt allele was performed by polymerase chain reaction and Hinf I digestion of genomic DNA extracted from whole blood.4 The tt genotype was present in 9-6% (n = 18) of the patients with Parkinson's disease and 7-1% (n = 13) of the controls. In the Parkinson's disease group the heterozygote frequency was 42-5% (n = 80) and the non-thermola-bile homozygote frequency was 47-9% (n = 90). The corresponding frequencies in the control group were 47-3 % (n = 87) and 45-6% (n = 84) respectively. There was no significant difference in the frequency distribution of genotypes (x2 = 1-26, 2df, P = 0 53) and the odds ratio for the tt genotype was 1-39 (95% confidence intervals 0-63-3-12). These results clearly indicate that the tt genotype is not associated with Parkinson's disease and does not explain the finding that patients with Parkinson's disease are at increased risk of vascular disease. The fact that no association is found may indicate that the brain is protected from raised …