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Impact of PPAR-Alpha Polymorphisms—The Case of Metabolic Disorders and Atherosclerosis

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20122 Milan, Italy
Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, 20122 Milan, Italy
Multimedica, IRCCS, 20122 Milan, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4378;
Received: 26 July 2019 / Revised: 1 September 2019 / Accepted: 4 September 2019 / Published: 6 September 2019
(This article belongs to the Special Issue PPARs in Metabolic Regulation: Implications for Health and Disease)
Peroxisome proliferator activated receptor α (PPARα) has the most relevant biological functions among PPARs. Activation by drugs and dietary components lead to major metabolic changes, from reduced triglyceridemia to improvement in the metabolic syndrome. Polymorphisms of PPARα are of interest in order to improve our understanding of metabolic disorders associated with a raised or reduced risk of diseases. PPARα polymorphisms are mainly characterized by two sequence changes, L162V and V227A, with the latter occurring only in Eastern nations, and by numerous SNPs (Single nucleotide polymorphisms) with a less clear biological role. The minor allele of L162V associates with raised total cholesterol, LDL-C (low-density lipoprotein cholesterol), and triglycerides, reduced HDL-C (high-density lipoprotein metabolism), and elevated lipoprotein (a). An increased cardiovascular risk is not clear, whereas a raised risk of diabetes or of liver steatosis are not well supported. The minor allele of the V227A polymorphism is instead linked to a reduction of steatosis and raised γ-glutamyltranspeptidase levels in non-drinking Orientals, the latter being reduced in drinkers. Lastly, the minor allele of rs4353747 is associated with a raised high-altitude appetite loss. These and other associations indicate the predictive potential of PPARα polymorphisms for an improved understanding of human disease, which also explain variability in the clinical response to specific drug treatments or dietary approaches. View Full-Text
Keywords: PPARα; polymorphism L162V; polymorphism Val227Ala; rs4253778 G > C; rs4253776 A > G PPARα; polymorphism L162V; polymorphism Val227Ala; rs4253778 G >; C; rs4253776 A >; G
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Ruscica, M.; Busnelli, M.; Runfola, E.; Corsini, A.; Sirtori, C.R. Impact of PPAR-Alpha Polymorphisms—The Case of Metabolic Disorders and Atherosclerosis. Int. J. Mol. Sci. 2019, 20, 4378.

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