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超氧化物歧化酶同工酶的浓度/活性及氧化应激状态与 2 型糖尿病和部分单核苷酸多态性(基因:INS、SOD1、SOD2、SOD3)的相关性——初步研究结果。

Concentration/activity of superoxide dismutase isozymes and the pro-/antioxidative status, in context of type 2 diabetes and selected single nucleotide polymorphisms (genes: INS, SOD1, SOD2, SOD3) - Preliminary findings.

机构信息

Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, Borowska Street 211, 50-556 Wrocław, Poland.

Department of Clinical Chemistry and Laboratory Hematology, Faculty of Pharmacy, Wroclaw Medical University, Borowska Street 211A, 50-556 Wrocław, Poland.

出版信息

Biomed Pharmacother. 2021 May;137:111396. doi: 10.1016/j.biopha.2021.111396. Epub 2021 Feb 23.

DOI:10.1016/j.biopha.2021.111396
PMID:33761612
Abstract

The alterations in concentration/activity of superoxide dismutase isozymes in the context of type 2 diabetes or obesity are well-described. Moreover, many hereditary factors, including single-nucleotide polymorphisms (SNPs) of genes for coding insulin, insulin receptors, or insulin receptor substrates (INS, INSR, IRS1, IRS2) or superoxide dismutase isozymes (SOD1, SOD2, SOD3), have been linked with the incidence of obesity and diabetes. However, the underlying changes in the plasma concentration/activity of superoxide dismutase isozymes and their potential connection with the said hereditary factors remain unexplored. Previously, we have observed that the plasma concentration/activity of superoxide dismutase isozymes differs in the context of obesity and/or rs2234694 (SOD1) and rs4880 (SOD2) and that the concentrations of SOD1, SOD2, SOD3 are correlated with each other. Intersexual variability of SOD1 concentration was detected regardless of obesity. In this study, the variability of concentration/activity of superoxide dismutase isozymes in plasma is considered in the context of type 2 diabetes and/or SNPs: rs2234694 (SOD1), rs5746105 (SOD2), rs4880 (SOD2), rs927450 (SOD2), rs8192287 (SOD3). Genotypic variability of SNP rs3842729 (INS), previously studied in the context of insulin-dependent diabetes, is investigated in terms of selected clinical parameters associated with type 2 diabetes. This study revealed higher SOD1 concentration in diabetic men compared to women, and extremely high SOD1 concentration, higher total superoxide dismutase, and copper-zinc superoxide dismutase activity, and lower superoxide dismutase and copper-zinc superoxide dismutase activity (when adjusted for the concentration of SODs) in the diabetic group regardless of sex. Multiple logistic regression, applied to explore possible links between the studied SNPs and other factors with the odds of type 2 diabetes or obesity, revealed that the genotypic variability of rs4880 (SOD2) could affect these odds, supporting the findings of several other studies.

摘要

超氧化物歧化酶同工酶在 2 型糖尿病或肥胖症中的浓度/活性变化已得到充分描述。此外,许多遗传因素,包括编码胰岛素、胰岛素受体或胰岛素受体底物(INS、INSR、IRS1、IRS2)或超氧化物歧化酶同工酶(SOD1、SOD2、SOD3)的单核苷酸多态性(SNP),与肥胖症和糖尿病的发生有关。然而,超氧化物歧化酶同工酶在血浆中的浓度/活性的潜在变化及其与上述遗传因素的潜在联系仍未得到探索。此前,我们观察到超氧化物歧化酶同工酶在肥胖症和/或 rs2234694(SOD1)和 rs4880(SOD2)的背景下血浆浓度/活性不同,并且 SOD1、SOD2、SOD3 的浓度彼此相关。无论肥胖与否,都检测到 SOD1 浓度的两性差异。在这项研究中,考虑了 2 型糖尿病和/或 SNP 的背景下血浆中超氧化物歧化酶同工酶浓度/活性的变异性:rs2234694(SOD1)、rs5746105(SOD2)、rs4880(SOD2)、rs927450(SOD2)、rs8192287(SOD3)。先前在胰岛素依赖型糖尿病背景下研究过的 SNP rs3842729(INS)的基因型变异性,根据与 2 型糖尿病相关的选定临床参数进行了研究。这项研究表明,与女性相比,糖尿病男性的 SOD1 浓度更高,无论性别如何,糖尿病组的 SOD1 浓度极高,总超氧化物歧化酶和铜锌超氧化物歧化酶活性更高,超氧化物歧化酶和铜锌超氧化物歧化酶活性更低(当根据 SOD 浓度进行调整时)。应用多元逻辑回归探索研究 SNP 与其他因素与 2 型糖尿病或肥胖几率之间可能的联系表明,rs4880(SOD2)的基因型变异性可能会影响这些几率,这支持了其他几项研究的发现。

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