A plasma proteomics method reveals links between ischemic stroke and MTHFR C677T genotype

Methylene Tetrahydrofolate Reductase (MTHFR) catalyzes the conversion of methylene tetrahydrofolate to methylte trahydrofolate. The 677th nucleotide of the MTHFR gene is often regarded as a risk factor of cardiovascular disease. Previous studies demonstrated an elevated risk of ischemic stroke with the MTHFR677TT genotype. In this study, we employed a plasma proteomics method to investigate the connection between the polymorphism of the target nucleotide and stroke. In total, 28 protein spots were differentially expressed between the two groups, and of which, 25 protein spots were up-regulated and 3 were down-regulated. Five randomly selected spots were successfully identified as Haptoglobin (HPT) and Transferrin (TRFE). A functional analysis indicated that most of the differential expressed proteins (DEPs) were related to the inflammatory immune response. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEPs were involved in the complement cascade reaction. Meanwhile, protein-protein interactions (PPIs) analysis highlighted the novel association between the C677T MTHFR genotype and Vitamin D binding protein (DBP), which was confirmed by a molecular genetic analysis. The results suggested that the phenotype of the MTHFR might be associated with multiple proteins that have a synergistic effect, which might be related to the mechanism of ischemic stroke.