Association of tissue factor A-603G genotype with carotid intima-media thickness in subjects in cardiovascular risk prevention

Introduction: Tissue factor (TF), key initiator of coagulation, is also ascribed a non-hemostatic function in atherosclerosis development. Polymorphisms in the TF gene promoter have been shown to modulate the expression of TF, and thus perhaps also its role in atherosclerosis. Hence, this study investigated associations between TF promoter genotype and carotid intima-media thickness (IMT), a well-established marker of atherosclerosis. Methods: The TF A-603G polymorphism and carotid IMT was analysed in 324 patients undergoing primary and secondary cardiovascular risk prevention. Also, the TF Del-1208Ins polymorphism was investigated in 84 subjects, confirming the previously reported complete concordance between the -603A and -1208Del alleles. Subjects were 60.5±8.4 years old, 80% were male, and 77% were undergoing secondary prevention with a history of atherosclerotic disease. Results: Both mean and maximum carotid IMT (measured at the common carotid, bifurcation, and internal carotid) differed significantly according to A-603G genotype, being highest in -603A/A (n=95), intermediate in A/G (n=164) and lowest in G/G (n=65) (mean IMT: A/A 1.31±0.37mm, A/G 1.28±0.33mm, G/G 1.22±0.35mm; max IMT: A/A 2.35±0.91mm, A/G 2.25±0.84mm, 2.15±0.97mm; both p<0.05; tested for trend; adjusted for age, gender, smoking habits, and anti-hypertensive treatment. Conclusions: In summary, a significant association between TF promoter genotype and carotid IMT was observed, maybe mediated via altered TF expression levels in the circulation or within the carotid vessel wall. These findings support a role of TF not only in thrombotic complications of atherosclerotic disease, but also in atheroma development.