Thrombospondin-4 polymorphism (A387P) predicts cardiovascular risk in postinfarction patients with high HDL cholesterol and C-reactive protein levels

James P. Corsetti, Dan Ryan, Arthur J. Moss, Jeanette J. Mccarthy, Ilan Goldenberg, Wojciech Zareba, Charles E. Sparks

Research output: Contribution to journalArticlepeer-review

Abstract

Few studies are available in human populations investigating involvement of vascular inflammation and oxidative stress-related dysfunctional transformation of high-density lipoprotein (HDL) in establishing cardiovascular disease (CVD) risk. To this end, the current work investigated a subgroup of post-infarction patients at high-risk for recurrent events defined by high levels of HDL cholesterol (HDL-C) and concurrently high levels of C-reactive protein (CRP). Thrombospondin-4 (TSP-4), a matricellular protein of vessel walls associated with inflammation, was investigated in terms of CVD risk using multivariable modelling with a well-characterised functional genetic polymorphism of THBS4 (A387P, rs1866389) along with previously demonstrated risk-related functional genetic polymorphisms of CYBA (C242T, rs4673) and CETP (TaqIB, rs708272), and a set of blood markers. Results revealed risk-association for the gain-of-function P-allele of the THBS4 polymorphism (hazard ratio 2.00, 95% confidence interval 1.10-3.65, p=0.024). Additionally, von Willebrand factor was associated with D-dimer levels in the higher-risk P allele patients suggestive of a connection between endothelial dysfunction and thrombogenesis. In conclusion, TSP-4, a matricellular protein involved in regulating vascular inflammation, plays a role in establishing recurrent coronary risk in postinfarction patients with high levels of HDL-C and CRP. Further studies should focus on additional effects of vascular inflammatory processes on anti-atherogenic functionality of HDL particles.

Original languageEnglish
Pages (from-to)1170-1178
Number of pages9
JournalThrombosis and Haemostasis
Volume106
Issue number6
DOIs
StatePublished - 2011
Externally publishedYes

Funding

FundersFunder number
National Heart, Lung, and Blood InstituteP01HL045522

    Keywords

    • C-reactive protein
    • HDL cholesterol
    • Inflammation
    • Oxidative stress
    • Thrombospondin-4

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