Association of Hyperhomocysteinemia and MTHFR Genotype in Parkinson's Disease

ABSTRACT

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) deficiency is rare in severe cases but common in mild cases. TT genotype of C677T of MTHFR shows reduced enzyme activity and hyperhomocysteinemia. It has been shown that homocysteine is very toxic to dopaminergic neuronal cell in vitro and animal experiment, which suggests some role of homocysteine in the pathogenesis of Parkinson's disease (PD). This study examined the association of MTHFR genotype, hyperhomocysteinemia, and Parkinson's disease. METHODS: Serum homocysteine concentration and the C677T genotypes of MTHFR were assessed in 80 patients with Parkinson's disease, and 80 healthy subjects matched for age and gender, in a hospital-based setting. RESULTS: Proportion of moderate hyperhomocysteinemia (plasma homocyst(e)ine > or =15 micromol/L) was higher in patients with Parkinson's disease than in normal controls (53.7% vs 30.0%, p=0.01). TT genotype of MTHFR was highly frequent in Parkinson's disease patients compared to controls (18.7% vs 11.3%, p=0.01). The combination of hyperhomocysteinemia and TT genotype of MTHFR augmented risk for Parkinson's disease (odds ratio 2.53 [95% confidence interval, 1.48-4.31, p=0.01]). CONCLUSIONS: Hyperhomocysteinemia is a common finding in the patients with Parkinson's disease. TT genotype of MTHFR is at increased risk for Parkinson's disease, and in conjunction with hyperhomocyeteinemia, augments the association.