Paraoxonase gene polymorphisms, oxidative stress, and diseases

Abstract

The paraoxonase (PON) gene cluster contains at least three members, including PON1, PON2, and PON3, located on chromosome 7q21.3-22.1. Until now there has been little insight into the role of the respective gene products in human physiology and pathology. However, emerging evidence from biochemical and genetic experiments is providing clues about the role(s) of the products of these genes, which indicates that PON(s) acts as important guardians against cellular damage from toxic agents, such as organophosphates, oxidized lipids in the plasma low-density lipoproteins. In parallel, substantial data have been published on the association between the polymorphisms of PON(s) and coronary heart disease. It has become clear that the polymorphisms significantly affect the prevalence of coronary heart disease. However, the associations between the PON(s) polymorphisms and most of these conditions were found to be inconsistent when additional populations were investigated. This contribution provides an overview of the status of research of each of the three genes and the available association studies and the potential problems in interpreting the data. We also review the current evidence on the association between PON(s) polymorphisms and diseases other than coronary heart disease and some metabolic quantitative phenotypes, such as plasma lipoproteins, plasma glucose, and birthweight. Finally, we suggest directions for the future that might elucidate the role of the PON genetic polymorphisms in this potentially important function of PON(s) and the role in coronary heart disease and other related diseases.

Paraoxonase-1 gene in patients with chronic obstructive pulmonary disease investigation Q192R and L55M polymorphisms

“…There was a difference in paraoxonase enzyme activities that were associated with polymorphism. [10] Moreover, there were signifi cant differences in paraoxonase activities related to Q192R and L55M polymorphism. [11] And QQ genotype expressed lowest enzyme activity, while QR and RR genotypes expressed moderate and highest enzyme activities, respectively.…”

Increased methionine sulfoxide content of apoA-I in type 1 diabetes

“…Once LPOs are absorbed by HDL, they are either transported to the liver, where they are detoxified and excreted into the bile (13)(14)(15), or they are reduced directly by HDL to hydroxylipids (16,17). At least two HDL-bound proteins are involved with LPO detoxification, paraoxonase (PON-1) (18,19) and apolipoprotein A-I (apoA-I) (20). PON-1 is a lactonase that protects against LDL and HDL oxidation by hydrolyzing oxidized fatty acids to lactones; plasma or serum PON-1 concentration or activity is inversely correlated with CVD and is commonly decreased in diabetes and in renal disease (21)(22)(23)(24).…”

Estudo das paraoxonases 1, 2 e 3 em pacientes portadores de anemia falciforme"

“…O gene da PON2 expressa uma proteína intracelular, com peso molecular de aproximadamente 43 kDa Horke et al, 2008), distribuída por 9 éxons, 8 íntrons e 355 aminoácidos (Li et al, 2003).…”

“…O polimorfismo localizado na posição 148, do gene da PON2, encontra-se associado às variações de lipoproteínas (Boright et al, 1998;Li et al, 2003) e níveis de glicose basal, no plasma, em portadores de diabetes mellitus tipo 2 (Hegele et al, 1997;Beer et al, 2006). O genótipo 148GG…”

“…A aparente função desta proteína seria fornecer uma ateroproteção constitutiva basal, sendo necessários maiores estudos in vivo visando determinar se a sua atividade estaria envolvida, ou não, na prevenção da aterosclerose (Li et al, 2003). Draganov e colaboradores (2000) demonstraram que a PON3 sérica de coelho também está fortemente associada à fração HDL, apresentando ação lactonase e sendo cerca de 100…”