COMT, MTHFR and SLC19A1(RFC-1) Polymorphisms, Homocysteine Blood Levels and Cognitive Impairment in Parkinson 's Disease (P04.175)

OBJECTIVE: The study evaluated relationships between Hcy, vitamin B12 and folic acid blood levels, and cognitive status in PD with polymorphisms of MTHFR, COMT and SLC19A1 genes. BACKGROUND: The role of homocysteine (Hcy) and folate in the pathogenesis of Parkinson disease (PD) remains controversial. DESIGN/METHODS: A total of 248 PD and 254 age and sex matched controls were included. UPDRS, H-Y staging and the Schwab-England scale were used to assess motor abilities and activity. Complex psychological examination was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples for Hcy, vitamin B12, folic acid as well as polymorphisms in genes related to Hcy metabolism: COMT, MTHFR, SLC19A1(RFC-1) were examined. RESULTS: The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD in comparison with controls (p=0.015; OR= 0.60; 95%CI 0.41-0.90 and p=0.020; OR 0.619; 95%CI 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C/T, 1298A/C and SLC19A1 80G/A alleles and genotypes between PD and controls were found. Hcy levels were significantly increased in PD (18+/-7.8 mcM) as compared to the control subjects (14.0+/-9.6 mcM, p=10-8), and were significantly associated with the MTHFR 677C/T polymorphism both in PD and controls, where T allele carriers were characterized by markedly elevated Hcy. No association was observed between Hcy and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (p=0.0003) and Hcy (p=0.07) as independent risk factors predisposing to PD dementia. The studied polymorphisms were not associated with cognitive status in PD. CONCLUSIONS: The genetic factors studied were not associated with cognitive status in PD. Only age and homocysteine plasma levels were found to be independent risk factors predisposing to PD dementia. COMT:rs4680:A/G and rs4633:C/T polymorphisms were found to significantly affect PD risk, and MTHFR 677C/T to determine plasma homocysteine concentrations. Disclosure: Dr. Bialecka has received personal compensation for activities with Novartis and GlaxoSmithKline, Inc. Dr. Drozdzik has nothing to disclose. Dr. Kurzawski has nothing to disclose. Dr. Sitek has nothing to disclose. Dr. Golab-Janowska has nothing to disclose. Dr. Honczarenko has nothing to disclose. Dr. Mak has nothing to disclose. Dr. Robowski has nothing to disclose. Dr. Roszman has nothing to disclose. Dr. Slawek has received personal compensation for activities with GlaxoSmithKline and Novartis.