Importance of Polymorphisms in the Gene of Paraoxonase-1 (SNP rs662) and Apolipoprotein A-I (SNP rs670 and rs5069) in Non-Smoking and Smoking Healthy Subjects and Patients with Acute Pancreatitis

Abstract

Oxidative stress has been implicated in the initiation of acute pancreatitis (AP). HDL is considered to be a preventing factor against cell membrane oxidation, thanks to the presence on its surface of apolipoprotein A-I (apoA-I) and paraoxonase-1 (PON1), which activity can be modified by genetic and environmental factors. The impact of SNP rs662 in the PON1 gene and SNP rs670 and rs5069 in the APOAI gene on PON1 activities and its concentration in the population of AP patients and healthy volunteers was investigated. In the group of patients with AP, a decreased HDL concentration and PON1 activities were observed. A decrease in the aryloesterase and lactonase activities of PON1 in AP patients with the TT genotype for SNP rs662 (especially in smokers) was found. In the group of patients with the AA genotype (rs670), the highest concentrations of HDL and apoA-I were observed, which were gradually decreasing in the course of AP. Changes in the concentration of apoA-I were associated with the changes in the concentration and activities of PON1 in the AP patients with the AA genotype for SNP rs670. A decreasing apoA-I concentration contributing to lowering PON1 concentration and its activities during the hospitalization of AP patients with the CC genotype for SNP rs5069 were shown. Therefore, more susceptibility of persons with the CC genotype for SNP rs5069 to pro/antioxidative imbalance was shown. In this process, an important role was played by the HDL level and its interaction with PON1 and apoA-I.

Association of APOE (rs429358 and rs7412) and PON1 (Q192R and L55M) Variants with Myocardial Infarction in the Pashtun Ethnic Population of Khyber Pakhtunkhwa, Pakistan

“…[ 27 , 28 ]. Similarly, PON1 is a membrane-bound glycoprotein encoded by the PON1 gene that is located on chromosome 7q21.3-q22.1 [ 29 , 30 ]. It is associated with highly-density lipoprotein (HDL) and is found in a variety of tissues but is predominantly synthesized in the liver [ 31 ].…”

“…It inhibits the concentration of low-density lipoprotein cholesterol (LDL-C) by hydrolysis of lipid peroxides [ 31 ]. PON1 has considerable anti-inflammatory and anti-oxidative actions through its enzymatic Paroxonase, lactonase, and esterase activities [ 29 ]. There is some evidence of low serum PON1 activity in patients with lipid disorders such as diabetes mellitus (DM), MI, atherosclerosis, and familial hypercholesterolemia [ 30 ].…”

Anti-inflammatory mechanism of Apolipoprotein A-I

“…In particular, polymorphisms at the -75 bp locus of the ApoA-I gene have been linked to an increased risk of myocardial infarction in these patients ( 17 ). Individuals with the CC genotype of SNP rs5069 are more susceptible to oxidative imbalance and are at a higher risk of developing pancreatitis ( 18 ).…”