Open Access

Evaluation of the role of Nrf2/Keap1 pathway‑associated novel mutations and gene expression on antioxidant status in patients with deep vein thrombosis

  • Authors:
    • Di̇lara Fatma Akin‑Bali
    • Tamer Eroglu
    • Sedef Ilk
    • Yonca Egi̇n
    • Teoman Kankilic
  • View Affiliations

  • Published online on: May 25, 2020     https://doi.org/10.3892/etm.2020.8790
  • Pages: 868-881
  • Copyright: © Akin‑Bali et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Deep vein thrombosis (DVT) is a type of venous thromboembolism and a clinically complex vascular disease. Oxidative stress serves a key role in the pathogenesis of numerous cardiovascular diseases, particularly in endothelial dysfunction‑associated syndromes. Nuclear factor erythroid‑2‑like 2(Nrf2) transcription factor is the primary regulator of antioxidant responses. The levels of reactive oxygen species (ROS) are regulated by Nrf2 and its suppressor protein Kelch‑like ECH‑associated protein 1 (Keap1). However, to the best of our knowledge, genetic abnormalites in the Nrf2/Keap1 pathway in DVT syndrome have not been thoroughly investigated. The aim of the present study was to investigate the association between the Nrf2/Keap1 pathway and antioxidant responses in DVT. Mutations and expression levels of genes involved in the Nrf2/Keap1 pathway were measured in 27 patients with DVT via DNA sequencing analysis and reverse transcription‑quantitative PCR, respectively. The Polymorphism Phenotyping v2 program was used to identify the pathogenic mutations. Total antioxidant activity levels were determined by measuring the effect of serum samples from 27 patients with DVT on oxidation of the 2,2'‑azino‑bis (3‑ethylbenz‑thiazoline‑6‑sulfonic acid) system. A total of 23 mutations, including seven novel mutations, were detected in the Nrf2/Keap1 pathway in 24 (89%) of the 27 patients with DVT. Keap1 mRNA expression levels were significantly higher compared with Nrf2 expression levels in patients with DVT (P=0.02). Analysis of molecular characteristics and gene expression levels demonstrated that Nrf2/Keap1‑associated mutations and total antioxidant levels can be used as precursor markers in the diagnosis of DVT.

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August-2020
Volume 20 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Akin‑Bali DF, Eroglu T, Ilk S, Egi̇n Y and Kankilic T: Evaluation of the role of Nrf2/Keap1 pathway‑associated novel mutations and gene expression on antioxidant status in patients with deep vein thrombosis. Exp Ther Med 20: 868-881, 2020
APA
Akin‑Bali, D.F., Eroglu, T., Ilk, S., Egi̇n, Y., & Kankilic, T. (2020). Evaluation of the role of Nrf2/Keap1 pathway‑associated novel mutations and gene expression on antioxidant status in patients with deep vein thrombosis. Experimental and Therapeutic Medicine, 20, 868-881. https://doi.org/10.3892/etm.2020.8790
MLA
Akin‑Bali, D. F., Eroglu, T., Ilk, S., Egi̇n, Y., Kankilic, T."Evaluation of the role of Nrf2/Keap1 pathway‑associated novel mutations and gene expression on antioxidant status in patients with deep vein thrombosis". Experimental and Therapeutic Medicine 20.2 (2020): 868-881.
Chicago
Akin‑Bali, D. F., Eroglu, T., Ilk, S., Egi̇n, Y., Kankilic, T."Evaluation of the role of Nrf2/Keap1 pathway‑associated novel mutations and gene expression on antioxidant status in patients with deep vein thrombosis". Experimental and Therapeutic Medicine 20, no. 2 (2020): 868-881. https://doi.org/10.3892/etm.2020.8790