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

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.

[The antioxidant function of high density lipoproteins: a new paradigm in atherosclerosis]. / Función antioxidante de las lipoproteínas de alta densidad: un nuevo paradigma en la arteriosclerosis.

The one disease associated with the greatest morbidity and mortality in industrialized countries is coronary heart disease (CHD). High density lipoprotein (HDL) is one of the most important independent protective factors for the arteriosclerosis which underlies CHD. Paraoxonase 1 (PON1) is an enzyme that confers antioxidant properties to HDL. In vitro, PON1 hydrolyzes a large variety of endogenous or exogenous substrates, some of which are clearly involved in the progression of arteriosclerosis. A close relationship between PON1 deficiency and accelerated progression of arteriosclerosis has been found in animal models. Moreover, PON1 activity is reduced in high oxidative stress diseases such as CHD, dyslipoproteinemias, inflammatory processes, diabetes and certain neuropathies. Reduced PON1 enzyme activity is associated with several arteriosclerosis-related diseases. The most thoroughly studied genetic variant of PON1 is PON1-192, in which the R allele is associated with elevated paraoxonase activity. This allele, present in 24.8% of the Italian population, is found in up to 78.9% of the population of Ecuadorian Cayapa Indians. A metaanalysis of studies on the relationship between CHD and the R allele showed the latter to be an independent risk factor for this disease, with an odds ratio of 1.18 (95% confidence interval, 1.10-1.27). The PON1 enzyme is a potentially useful new qualitative indicator in addition to the well known reverse cholesterol transport capacity associated with high plasma levels of HDL.