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

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Research
• Proteomics

Background:

• The MTHFR gene's 677th nucleotide polymorphism is linked to cardiovascular disease risk.
• Previous research indicates an increased risk of ischemic stroke with the MTHFR677TT genotype.

Purpose of the Study:

• To investigate the association between MTHFR gene polymorphism and stroke using plasma proteomics.
• To identify differentially expressed proteins (DEPs) and their pathways in relation to MTHFR genotype.

Main Methods:

• Plasma proteomics analysis to compare protein expression between MTHFR genotype groups.
• Protein identification, functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) analysis.
• Molecular genetic analysis to confirm genotype-protein associations.

Main Results:

• 28 differentially expressed protein spots were identified, with 25 up-regulated and 3 down-regulated.
• Haptoglobin (HPT) and Transferrin (TRFE) were among the identified proteins.
• DEPs were predominantly involved in inflammatory immune responses and the complement cascade.
• A novel association was found between the MTHFR C677T genotype and Vitamin D binding protein (DBP).

Conclusions:

• The MTHFR gene polymorphism is associated with a distinct plasma proteomic profile.
• These proteomic changes, particularly those related to inflammation and complement pathways, may contribute to the mechanism of ischemic stroke.
• The identified associations, including the novel link with DBP, warrant further investigation into MTHFR's role in stroke pathogenesis.