The Relevance of Noncoding DNA Variations of Paraoxonase Gene Cluster in Atherosclerosis-Related Diseases.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Multigene Family*; Aryldialkylphosphatase/*genetics ; Atherosclerosis/*enzymology ; Atherosclerosis/*genetics ; DNA, Intergenic/*genetics; Animals ; Atherosclerosis/blood ; Humans ; Lipids/blood ; Polymorphism, Genetic

The human paraoxonase ( PON ) gene cluster is comprised of three contiguous genes ( PON1, PON2 and PON3 ) of presumably common origin coding three lactonases of highly similar structure and substrate specificity. The catalytic activity of PON proteins is directed toward artificial organophosphates and in physiological conditions toward thiolactones and oxidized phospholipids. Consequently, PON enzymes are regarded as an effective defense against oxidative stress and, as a result, against atherosclerosis development. Additionally, both PON's serum activity and its concentration are influenced by several polymorphic variations in coding and noncoding DNA regions of the PON gene cluster remaining in linkage disequilibrium. Hence, the genetic polymorphism of the PON gene cluster may contribute to atherosclerotic process progression or deceleration. In this review the authors analyzed the relevance of noncoding DNA polymorphic variations of PON genes in atherosclerosis-related diseases involving coronary and peripheral artery disease, stroke, diabetes mellitus, dementia and renal disease and concluded that the effect of PON gene cluster' polymorphism has a considerable impact on the course and outcome in these conditions. The following PON genetic variations may serve as additional predictors of the risk of atherosclerosis in selected populations and individuals.

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Keywords: atherosclerosis; paraoxonase; polymorphism

0 (DNA, Intergenic)
0 (Lipids)
EC 3.1.8.1 (Aryldialkylphosphatase)

Date Created: 20210306 Date Completed: 20210413 Latest Revision: 20210413

20221213

PMC7926863

10.3390/ijms22042137

33670025