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

Deep vein thrombosis (DVT) affects vascular health and can even threaten life; however, its pathogenesis remains unclear. Cardiovascular disease (CVD) and DVT share common risk factors, such as dyslipidemia, aging, etc. We aimed to investigate the loci of published CVD susceptibility genes and their association with environmental factors that might be related to DVT. Genotyping by Kompetitive Allele Specific PCR (KASP), collection of lifestyle information, and determination of blood biochemical markers were performed in 165 DVT cases and 164 controls. The impact of six single nucleotide polymorphisms (SNPs) and additional potential variables on DVT morbidity was evaluated using unconditional logistic regression (ULR). To explore the high-order interactions related to genetics and the body's internal environment exposure that affect DVT, ULR, crossover analysis, and multifactor dimensionality reduction/generalized multifactor dimensionality reduction (MDR/GMDR) were employed. Sensitivity analyses were performed using the EpiR package. The polymorphisms of FGB rs1800790 and PLAT rs2020918 were significantly associated with DVT. The optimum GMDR interaction model for gene-gene (G × G) consisted of THBD rs1042579, PLAT rs2020918, and PON1 rs662. The PLAT rs2020918 and MTHFR rs1801133 polymorphisms together eliminated the maximum entropy by the MDR method. The optimum GMDR interaction model for gene-environment (G × E) consisted of MTHFR rs1801133, FGB rs1800790, PLAT rs2020918, PON1 rs662, and total homocysteine (tHcy). Those with high tHcy levels and three risk genotypes significantly increased the DVT risk. In conclusion, certain CVD-related SNPs and their interactions with tHcy may contribute to DVT. These have implications for investigating DVT etiology and developing preventive treatment plans.
Competing Interests: The authors declare no competing financial interest.
(© 2024 The Authors. Published by American Chemical Society.)