Association of seven functional polymorphisms of one-carbon metabolic pathway with total plasma homocysteine levels and susceptibility to Parkinson's disease among South Indians

摘要

This study from South India was performed to ascertain the impact of seven functional polymorphisms of one-carbon metabolic pathway on total plasma homocysteine levels and susceptibility to PD. A total of 151 cases of Parkinson's disease and 416 healthy controls were analyzed for fasting plasma homocysteine levels by reverse phase HPLC PCR-RFLP approaches were used to analyze glutamate carboxypeptidase II (GCPII) 1561 OT, reduced folate carrier 1 (RFC1) 80 G>A, cytosolic serine hydroxymethyl transferase (cSHMT) 1420 OT, methylene tetrahydrofolate reductase (MTHFR) 677 OT, methionine synthase (MTR) 2756 A>G and methionine synthase reductase (MTRR) 66 A>G polymorphisms. PCR-AFLP was used for the analysis of thymidylate synthase (TYMS) 5'-UTR 28 bp tandem repeat. PD cases exhibited elevated plasma homocysteine levels compared to controls (men: 28.8 ±6.9 vs. 16.4 ±8.8 mumol/L; women: 25.4 ±5.3 vs. 11.2±5.1 |jimol/L). Homocysteine levels showed positive correlation with male gender (r=0.39, p < 0.0001) and MTRR 66 A>G (r= 0.31, p < 0.0001) whereas an inverse correlation was observed with cSHMT 1420 OT polymorphism. MTRR 66 A>G polymorphism showed independent risk for PD (OR: 3.42, 95% CI: 2.35-4.98) whereas cSHMT 1420 OT conferred protection against PD (OR: 0.11, 95% CI: 0.07-0.17). Multifactor dimensionality reduction analysis showed synergistic interactions between MTHFR 677 OT and MTRR 66 A>G, whereas cSHMT 1420 OT exhibited counteracting interactions in altering susceptibility to PD. To conclude, PD cases exhibited hyperhomocysteinemia and MTRR 66 A>G and cSHMT 1420 OT gene variants were shown to modulate PD risk by altering the homocysteine levels.