The Impact of Cardiovascular Disease Gene Polymorphism and Interaction with Homocysteine on Deep Vein Thrombosis

Area of Science:

• Genetics and Molecular Biology
• Vascular Health and Thrombosis
• Biochemistry and Environmental Health

Background:

• Deep vein thrombosis (DVT) is a serious vascular condition with unclear pathogenesis.
• Shared risk factors exist between DVT and cardiovascular disease (CVD), including dyslipidemia and aging.
• Investigating the genetic links between CVD susceptibility and DVT is crucial for understanding disease mechanisms.

Purpose of the Study:

• To examine the association between established CVD susceptibility gene loci and DVT.
• To explore the interaction between genetic factors and environmental exposures in DVT development.
• To identify specific single nucleotide polymorphisms (SNPs) and biomarkers contributing to DVT risk.

Main Methods:

• Genotyping using Kompetitive Allele Specific PCR (KASP) for six SNPs in 165 DVT cases and 164 controls.
• Collection of lifestyle information and blood biochemical markers, including total homocysteine (tHcy).
• Unconditional logistic regression (ULR), crossover analysis, and multifactor dimensionality reduction (MDR/GMDR) for interaction analysis.

Main Results:

• Polymorphisms in FGB rs1800790 and PLAT rs2020918 were significantly associated with DVT.
• Optimal gene-gene (G × G) interaction models involved THBD rs1042579, PLAT rs2020918, and PON1 rs662.
• An optimal gene-environment (G × E) model identified MTHFR rs1801133, FGB rs1800790, PLAT rs2020918, PON1 rs662, and tHcy as significant contributors; high tHcy with three risk genotypes markedly increased DVT risk.

Conclusions:

• Specific CVD-associated SNPs and their interactions with total homocysteine levels contribute to DVT pathogenesis.
• These findings highlight the importance of considering gene-environment interactions in DVT etiology.
• The study provides insights for developing targeted preventive strategies and treatments for deep vein thrombosis.