Division of Biomedical and Environmental Analyses, Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, 211A Borowska St., 50-556 Wroclaw, Poland.
Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211 St., 50-556 Wroclaw, Poland.
Genes (Basel). 2022 Oct 28;13(11):1968. doi: 10.3390/genes13111968.
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 gene and SNP rs670 and rs5069 in the 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.
氧化应激被认为与急性胰腺炎(AP)的发生有关。高密度脂蛋白(HDL)被认为是细胞膜氧化的预防因素,这要归功于其表面存在载脂蛋白 A-I(apoA-I)和对氧磷酶 1(PON1),其活性可以通过遗传和环境因素进行修饰。本研究旨在探讨 SNP rs662 基因和 SNP rs670、rs5069 基因对 AP 患者和健康志愿者群体中 PON1 活性及其浓度的影响。在 AP 患者组中,观察到 HDL 浓度和 PON1 活性降低。在 SNP rs662 的 TT 基因型(尤其是在吸烟者中)的 AP 患者中,PON1 的芳基酯酶和内酯酶活性降低。在 SNP rs670 的 AA 基因型(rs670)患者组中,观察到 HDL 和 apoA-I 的浓度最高,随着 AP 的发展逐渐降低。apoA-I 浓度的变化与 SNP rs670 的 AA 基因型的 AP 患者的 PON1 浓度和活性的变化相关。SNP rs5069 的 CC 基因型的 AP 患者中,apoA-I 浓度降低导致 PON1 浓度及其活性降低。因此,SNP rs5069 的 CC 基因型的个体更易发生促/抗氧化失衡。在这个过程中,HDL 水平及其与 PON1 和 apoA-I 的相互作用起着重要作用。