Abstract 1260: Genetic Variants in the Vitronectin (VTN) Gene and the Risk of Myocardial Infarction
Background: Vitronectin, a multifunctional glycoprotein with multiple binding domains, has been identified as a critical modulator of the physiological and phathological processes, including thrombosis, hemostasis, fibrinolysis, pericellular proteolysis, inflammation, cell adhesion, migration and vascular remodeling, all of which are involved in the pathogenesis of myocardial infarction (MI). We therefore investigated whether genetic variants in the vitronectin (VTN) gene might contribute to the risk of MI.
Methods: The association of variant rs2227728 (2891T>C) in the VTN gene with the risk of MI was determined in 2 independent case-control studies: one comprised of 322 patients with MI and 456 control subjects, and the other comprised of 312 patients and 545 control subjects. Because rs2227728 was in a linkage disequilibrium with two other promoter variants rs2227720 (−148T>C), rs2227721(−78G>T) (r2>0.85), which were located in a natural block of VTN gene, the function of VTN gene promoter variants was studied by using luciferase reporter assays.
Results: We found that tag SNP 2891T>C was significantly associated with risk of MI. In the first population, the odds ratio [OR] was 1.68 (95% confidence interval [CI] 1.22 to 2.31, P=0.001) under a dominant model and 1.53 (95% CI 1.22 to 2.31, P=0.001) under an additive model. In the second population, the OR was 1.58 (95% CI 1.08 to 2.3, P=0.017) under a dominant model and 1.52 (95% CI 1.1 to 2.1, P=0.011) under an additive model. The combined ORs were 1.64 (95% CI 1.08 to 2.3, P=2.2×10−5, under a dominant model) and 1.52 (95% CI 1.1 to 2.1, P=3.8×10−5, under an additive model). Luciferase reporter assays demonstrated that the linked −148C and −78T alleles-bearing VTN promoter exerted 44% higher transcriptional activity than −148T and −78G alleles-bearing VTN promoter in HepG2 cells.
Conclusions: Our findings indicate that the variants in the VTN gene might be novel genetic markers for the risk of MI.