Abstract
Paraoxonase type 1 (PON1) have emerged as predictor of coronary heart disease (CHD). To date it is not known if PON1 is a causal determinant of atherosclerosis. In mouse models and in vitro it has been shown that PON1 is functionally involved in atherosclerosis, as it inhibits both LDL-oxidation and atherosclerosis progression. In humans, it turned out to be more difficult to find evidence for causality, because epidemiological studies on PON1 levels and/or activity are sensitive methodological bias and confounding variables and do not distinguish between cause or consequence. PON1 genotype is fixed at conception and therefore not subject to most forms of bias, not affected by confounding variables and not a consequence of CHD. Therefore, a relationship between PON1 genotype and CHD would support causal involvement of PON1 in CHD.
In the past decades there have been a large number of studies on PON1 Q192R, L55M and C-107T genotype and CHD. A meta analysis of those studies showed no convincing relationship, indicating that there is currently no strong genetic support for causal involvement of PON1 in CHD
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Roest, M., Voorbij, H. (2008). PON1 Genotypes and Coronary Heart Disease. In: Mackness, B., Mackness, M., Aviram, M., Paragh, G. (eds) The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism. Proteins And Cell Regulation, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6561-3_9
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DOI: https://doi.org/10.1007/978-1-4020-6561-3_9
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