Dysregulated miRNA-375, IL-17, TGF-β, and Microminerals Are Associated with Calpain-10 SNP 19 in Diabetic Patients: Correlation with Diabetic Nephropathy Stages

糖尿病患者中失调的 miRNA-375、IL-17、TGF-β 和微量矿物质与钙蛋白酶-10 SNP 19 相关:与糖尿病肾病分期的相关性

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作者:Ghada M Ezzat, Nashwa Mostafa A Azoz, Randa A El Zohne, HebatAllah Abdellatif, Tahia H Saleem, Wafaa Abdelaziz Emam, Amena Rezk Mohammed, Shimaa Ali Mohamed, Asmaa A Muhammed, Nessren M Abd El-Rady, Marwa Hamdy, Hoda S Sherkawy, Marwa A Sabet, Salwa Seif Eldin, Marwa A Dahpy

Abstract

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-β and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-β, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-β, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-β, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-β, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-β, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

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