Association of Nuclear Factor Erythroid-2-Related Actor 2 Gene Polymorphisms with Diabetic Nephropathy in Chinese Patients

AIM: Nuclear factor erythroid-2-related factor 2 (NRF2) has emerged as a therapeutic target in many diseases. To explore this further, we evaluated the relationships between the −617C/A (rs6721961) polymorphisms within the NRF2 promoter and diabetic nephropathy (DN) in Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 883 subjects with T2DM (500 without and 383 with DN) were enrolled in this study. Multivariable linear regression models were carried out to assess the association of DN with the −617C/A (rs6721961) polymorphisms. RESULTS: The AA genotype frequencies in patients with DN were significantly lower than those in patients without DN (χ(2) = 8.04, p = 0.018). Multivariate logistic regression analyses showed that individuals with the AA genotype had a significantly lower risk for DN (OR 0.52; 95% CI 0.28, 0.94; p = 0.029) than those with the CC genotype. Moreover, AA carriers had a significantly lower risk of DN (OR 0.46; 95% CI 0.26, 0.82; p = 0.009) relative to those with the CC + CA genotype, even after adjusting for known DN risk factors. CONCLUSION: Our study indicated that the −617C/A polymorphism within the NRF2 promoter was significantly associated with DN in Chinese Han patients with T2DM.