Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2021 May 27;22(11):5725. doi: 10.3390/ijms22115725.
This study was aimed at evaluating the changes in metallothionein (MT) concentration in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartments. The impact of single-nucleotide polymorphisms (SNPs) in the (rs11640851), (rs964372) and (rs10636) genes on MT concentration and their association with the concentration of metals (Cu, Zn, Cd) and ceruloplasmin as Cu-related proteins were analyzed. The concentration of a high-sensitivity C-reactive protein (hs-CRP) and IL-6 as markers of inflammation, and malonyldialdehyde (MDA), superoxide dismutase (SODs) activity and the value of total antioxidant capacity (TAC) as parameters describing the pro/antioxidative balance were also assessed. In the AP patient groups, an increased MT concentration in erythrocyte lysate compared to healthy subjects was shown, especially in individuals with the GG genotype for rs964372 in the gene. A Zn concentration was especially decreased in the blood of smoking AP patients with the AA genotype for SNP rs11640851 in the gene and the GC genotype for SNP rs10636 in MT2A, compared to non-smokers with AP, which was accompanied by an increase in the value of the Cu/Zn ratio. The exposure to tobacco smoke xenobiotics increased the risk of AP occurrence in subjects with the CC genotype for SNP rs11640851 in the gene by more than fourfold. The investigated polymorphisms, rs11640851 in the gene, rs964372 in the gene and rs10636 in the gene, seem to be an important factor in maintaining homeostasis in an organism under oxidative stress conditions.
本研究旨在评估急性胰腺炎(AP)患者和健康受试者血液中金属硫蛋白(MT)浓度的变化,同时考虑细胞外(血浆)和细胞内(红细胞裂解液)区室。分析了 (rs11640851)、 (rs964372)和 (rs10636)基因中单核苷酸多态性(SNP)对 MT 浓度的影响,及其与金属(Cu、Zn、Cd)和铜相关蛋白(如 ceruloplasmin)浓度的关系。还评估了高敏 C 反应蛋白(hs-CRP)和 IL-6 作为炎症标志物,以及丙二醛(MDA)、超氧化物歧化酶(SODs)活性和总抗氧化能力(TAC)值作为描述促/抗氧化平衡的参数。在 AP 患者组中,与健康受试者相比,红细胞裂解液中的 MT 浓度升高,尤其是在 基因中 rs964372 为 GG 基因型的个体中。与非吸烟者相比,携带 SNP rs11640851 的 AA 基因型和 SNP rs10636 的 GC 基因型的吸烟 AP 患者血液中的 Zn 浓度尤其降低,这伴随着 Cu/Zn 比值的增加。SNP rs11640851 在 基因中的 CC 基因型使接触烟草烟雾外源性化学物质的个体发生 AP 的风险增加了四倍以上。研究的多态性,即 基因中的 rs11640851、 基因中的 rs964372 和 基因中的 rs10636,似乎是维持氧化应激条件下机体内稳态的重要因素。