Evaluation of the relationship between two important diabetes complications and Nrf2 gene polymophisms
Project no. 20074 · Status: Kapanmış (Yayın bekleniyor) · 2018
Summary
<p>Introduction: Oxidative stress participates in the pathogenesis of microvascular complications of type 2 diabetes mellitus (T2DM). Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of antioxidant genes in response to oxidative stress. Polymorphisms in the promoter region of Nrf2 have been shown to be associated with various diseases. Our aim is to evaluate the association of rs35652124 (T>C), rs6706649 (G>A), rs6721961 (T>G) single nucleotide polymorphisms in the promoter region of the Nrf2 gene with diabetic nephropathy (DNP) and diabetic foot ulcers (DFU) in patients with T2DM. Methods: The study included 110 patients with DNP and 60 patients with DFU. As control group, diabetic patients without DNP and DFU (n=90) were enrolled. All patients had T2DM. After DNA isolation, single nucleotide polymorphisms were studied by polymerase chain reaction. Results: Patients in DNP group were older (p=0,039) and had longer duration of diabetes (p=0,042) than patients in control group. When compared to the control group, DNP group had lower estimated glomerular filtration rate (eGFR) (p<0,001) and higher albuminuria level (p<0,001). The genotype distribution of rs35652124 (T>C) and rs6721961 (T>G) was not different between patients with DNP and patients in the control group (p=0,192 and p=0,072, respectively). The distribution of rs6706649 (G>A) genotypes was statistically different among patients with DNP and the control group (p=0,048). When rs6706649 (G>A) polymorphism was evaluated, only GA genotype was shown to increase the risk of DNP (Exp(B)=2,888, 95% CI 0,160-7,189, p=0,023) when compared to GG genotype. Patients with DFU were older and had longer duration of diabetes than patients in the control group (p=0,013 and p=0,006, respectively). Patients with DFU had higher HbA1c, lower eGFR and higher albuminuria level when compared to the control group (p=0,003, p=0,001 and p<0,001, respectively). The frequencies of genotypes of rs35652124 (T>C), rs6706649 (G>A) and rs6721961 (T>G) were similar between patients with DFU and the control group (p=0,118, 0,625 and p=0,196, respectively). These polymorphisms were not associated with DFU. Conclusion: While rs6706649 (G>A) polymorphism GA genotype was a risk factor for DNP, no association was found between rs35652124 (T>C) and rs6721961 (T>G) polymorphisms and DNP. These polymorphisms were not associated with DFU.</p>