Promoter variants of VTN are associated with vascular disease

Abstract

Background: Vitronectin is involved in the whole process of atherosclerosis. Our aim is to determine the association of VTN functional promoter variants with different types of vascular disease, and conclude the roles of vitronectin involved in vascular disease.

Methods: Gel shift assays and luciferase reporter assays were used to determine the impact of variants on promoter activity. The correlation of plasma vitronectin levels with the variant was assessed in normal controls. The association of the variant with vascular disease was determined in 3 case-control studies.

Results: A strong linkage disequilibrium was found between rs2227721 and rs2227720 in VTN promoter in Chinese (r(2)=1.0). Both variants resulted in a decreased transcription activity, and rs2227721 decreased the binding efficiency of transcription factor YY1 to the region. The rs2227721 was correlated with plasma vitronectin levels in normal controls (r=-0.207, P=0.028). The rs2227721 was associated with susceptibility of vascular disease; the odds ratios among subjects carrying rs2227721-T allele were 1.298 (95% Confidence Interval-CI, 1.033-1.631) for non-MI CAD (P<0.05), 1.346 (95% CI, 1.068-1.695) for chronic MI (P<0.05), 1.486 (95% CI, 1.145-1.928) for acute MI (P<0.001), and 1.619 (95% CI, 1.108-2.366) for deep venous thrombosis (P<0.05).

Conclusion: VTN promoter haplotype would be a novel genetic marker for vascular disease.

Keywords: Coronary artery disease; Deep venous thrombosis; Genetic variation; Vascular disease; Vitronectin.