Relationship of classical and non-classical risk factors with genetic variants relevant to coronary heart disease

Abstract

BACKGROUND: In addition to the well established cardiovascular risk factors, evidence suggests a possible role of genetic and non-classical risk factors in the development and progression of atherothrombosis. We aimed to determine the relationship of classical and non-classical cardiovascular risk factors with candidate gene polymorphisms potentially involved in cardiovascular risk in the general Mediterranean population. DESIGN: Cross-sectional study. METHODS: We have determined the prevalence of classical (lipid profile, blood pressure, glycaemia, diabetes, smoking, body mass index, menopause and family history of coronary heart disease) and non-classical cardiovascular risk factors (infectious processes, homocysteinaemia, oxidative status, C-reactive protein, lipoprotein (a) and fibrinogen) in a population-based study. We analysed the relationship of these risk factors with the following five gene polymorphisms potentially involved in cardiovascular risk: ATP-binding cassette transporter A1-R219K, Peroxisome proliferator-activated receptor (PPAR)-alpha-L162V, Lipoprotein lipase (LPL)-HindIII, Paraoxonase (PON)1-Q192R, and Tumour necrosis factor (TNF)-alpha-G-308A. RESULTS: We found PPAR-alpha-V and LPL-H alleles to be associated with decreased high-density lipoprotein-cholesterol (HDL-c) concentration and with increased total cholesterol : HDL-c and triglyceride : HDL-c ratios. Regarding the non-classical risk factors, C-reactive protein concentration was higher for the PPAR-alpha-V allele. A higher oxidative status was shown in homozygotes for LPL-H and TNF-alpha-G alleles, although the latter also had lower homocysteinaemia. CONCLUSIONS: Three of the genetic variants analysed, PPAR-alpha-L162V, LPL-HindIII, and TNF-alpha-G-308A, were associated with non-classical risk factors, specifically lipid profile, inflammation, and oxidative status.