The association of KEAP1 and NFE2L2 polymorphisms with glycemic control and late complications in patients with type 2 diabetes

Vraničar, Zala (author), Goričar, Katja (author), Blagus, Tanja (author), Dolžan, Vita (author), Klen, Jasna (author)

To investigate the association of KEAP1 rs1048290, rs9676881 and NFE2L2 rs6706649, rs6721961, rs35652124 polymorphisms with glycemic control and development of late complications in patients with type 2 diabetes mellitus (T2DM), a total of 316 T2DM patients were included in the retrospective genetic association study. Genotyping was performed using competitive allele-specific PCR. Data on HbA1c levels as a measure of glycemic control, and information on late complications, including ischemic heart disease, retinopathy, and nephropathy, was obtained from the medical records. Logistic regression analysis was used to assess the association between selected genetic polymorphisms and patients outcomes. Significant associations were observed between KEAP1 rs9676881 (p < 0.001) and NFE2L2 rs6721961 (p = 0.006) polymorphisms and elevated HbA1c levels. Additionally, NFE2L2 rs35652124 polymorphism was linked to a nominally higher risk of late complications, including ischemic heart disease (p = 0.036), retinopathy (p = 0.032), and nephropathy (p = 0.026). Results indicate that polymorphisms in the KEAP1 and NFE2L2 genes may influence glycemic control and the development of late complications in T2DM patients. These findings provide valuable insights into the genetic factors underlying T2DM progression and its complications in European populations, highlighting the potential role of genetic markers in optimizing personalized treatment strategies.

• Language: English
• Keywords: diabetes mellitus type 2, oxidative pathway, genetic polymorphism, microvascular complications, macrovascular complications, personalized medicine
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 7 str.
• Numbering: Vol. 964, art. 149631
• PID: 20.500.12556/RUL-182545
• UDC: 616.3
• ISSN on article: 1879-0038
• DOI: 10.1016/j.gene.2025.149631
• COBISS.SI-ID: 240248579
• Publication date in RUL: 15.05.2026

Record is a part of a journal

• Title: Gene
• Shortened title: Gene
• Publisher: Elsevier
• ISSN: 1879-0038
• COBISS.SI-ID: 23394309

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0298
• Name: Geni, hormonske in osebnostne spremembe pri metabolnih motnjah