Association of Factor V Leiden (rs6025) Polymorphism with the Presence and Angiographic Severity of Coronary Artery Disease in a Pakistani Population: A Case–Control Study

Abstract

Objectives: This study aimed to investigate the association between Factor V Leiden (rs6025) polymorphism and the presence as well as angiographic severity of coronary artery disease in a Pakistani population. Methodology: This multi-institutional case–control study included 200 participants, comprising 100 angiographically confirmed CAD patients and 100 controls with normal coronary angiography. Biochemical parameters including lipid profile, fasting blood glucose, and fibrinogen levels were measured using standardized enzymatic and clot-based assays. Genotyping for Factor V Leiden rs6025 was performed using Amplification Refractory Mutation System–Polymerase Chain Reaction (ARMS-PCR). Results: The mutant A allele of the FVL rs6025 polymorphism was significantly more frequent in CAD patients compared with controls (OR = 3.79; 95% CI: 1.49–9.61; p = 0.005). Both heterozygous (GA: 15% vs. 4%) and homozygous mutant (AA: 3% vs. 1%) genotypes were observed more frequently among CAD cases than controls (p = 0.016). In addition, the presence of the mutant allele was significantly associated with multi-vessel coronary artery disease (p = 0.01), suggesting a relationship between FVL polymorphism and disease severity. CAD patients also demonstrated significantly higher blood pressure, fasting blood glucose, total cholesterol, LDL, VLDL, and fibrinogen levels, along with significantly lower HDL levels compared with controls. Conclusion: The findings of this study indicate that the Factor V Leiden (rs6025) polymorphism is significantly associated with both the presence and angiographic severity of coronary artery disease. The presence of the mutant A allele may contribute to increased thrombotic susceptibility and may act synergistically with conventional cardiovascular risk factors. Screening for this genetic polymorphism may improve risk stratification in individuals at high risk of CAD.