BACKGROUND: Influence of folate/homocysteine conversion is considered to be important in the pathogenesis of Parkinson's disease (PD). However, association of the folate metabolic pathway gene polymorphisms with PD susceptibility remains unclear. METHODS: To test this possibility in PD, we conducted a hospital-based case-control study constituting 211 patients and 218 age- and sex-matched controls of ethnic Chinese in Taiwan. Genotyping assay was performed to screen for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR A1049G and C1783T) genes and assess the association between these genotype polymorphisms and PD risk using logistic regression analysis. RESULTS: Of these four non-synonymous polymorphisms, the MTRR 1049GG variant was significantly associated with PD susceptibility (OR=3.17, 95%CI=1.08-9.35). Furthermore, we stratified our patients based on the MTHFR 677TT genotype in different strata, a significant association between the joint effect of polymorphisms and PD risk was observed in those patients whose genotypes were MTRR A1049G/MTR A2756G or MTRR C1783T/MTR A2756G (P<0.05). CONCLUSION: Our findings provide support for the synergistic effects of polymorphisms in the folate metabolic pathway genes in PD susceptibility; the increased PD risk would be more significant in carriers with the polymorphisms of MTHFR, MTR, and MTRR genes.
BACKGROUND: Influence of folate/homocysteine conversion is considered to be important in the pathogenesis of Parkinson's disease (PD). However, association of the folate metabolic pathway gene polymorphisms with PD susceptibility remains unclear. METHODS: To test this possibility in PD, we conducted a hospital-based case-control study constituting 211 patients and 218 age- and sex-matched controls of ethnic Chinese in Taiwan. Genotyping assay was performed to screen for polymorphisms of the methylenetetrahydrofolate reductase (MTHFRC677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRRA1049G and C1783T) genes and assess the association between these genotype polymorphisms and PD risk using logistic regression analysis. RESULTS: Of these four non-synonymous polymorphisms, the MTRR 1049GG variant was significantly associated with PD susceptibility (OR=3.17, 95%CI=1.08-9.35). Furthermore, we stratified our patients based on the MTHFR 677TT genotype in different strata, a significant association between the joint effect of polymorphisms and PD risk was observed in those patients whose genotypes were MTRR A1049G/MTR A2756G or MTRR C1783T/MTR A2756G (P<0.05). CONCLUSION: Our findings provide support for the synergistic effects of polymorphisms in the folate metabolic pathway genes in PD susceptibility; the increased PD risk would be more significant in carriers with the polymorphisms of MTHFR, MTR, and MTRR genes.
Authors: Nafisa M Jadavji; Lauren K Murray; Joshua T Emmerson; Chris A Rudyk; Shawn Hayley; Patrice D Smith Journal: Toxicol Sci Date: 2019-05-01 Impact factor: 4.849