Nrf2 and Keap1 Gene Polymorphisms and Lower Extremity Atherosclerosis in the Elderly

Objective: To investigate the association between Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) gene polymorphisms and lower extremity atherosclerotic disease (LEAD) in elderly individuals, and to develop a risk prediction model for LEAD. Methods: A total of 198 elderly inpatients diagnosed with lower extremity atherosclerosis by vascular ultrasound at the Affiliated Hospital of North Sichuan Medical College from November 2023 to November 2024 were enrolled as the case group. Sixty-six healthy individuals aged over 60 years without LEAD were randomly selected as controls. Polymorphisms at three gene loci (Nrf2 rs6721961, Nrf2 rs35652124, and Keap1 rs1048290) were analyzed using the TaqMan probe method. Various clinical indicators were included, and multiple logistic regression analyses were performed to construct prediction models. Results 1. Impact of gene polymorphisms on LEAD: Univariate analysis showed significant differences in genotype distributions of Nrf2 rs6721961 and Keap1 rs1048290 between cases and controls (P<0.05), while no significant difference was observed for Nrf2 rs35652124 (P>0.05). Logistic regression analysis indicated that carrying the TT genotype of Nrf2 rs6721961, along with a history of smoking and elevated LDL concentration, were significant risk factors for LEAD. 2. Evaluation of prediction model effectiveness: Among various constructed models, Model 3, which included the Nrf2 rs6721961 genotype, hypertension, smoking history, and LDL levels, showed better agreement between predicted and actual risk compared to models utilizing only genetic or clinical indicators. Model 3 effectively identified high-risk patients. Conclusion: 1. A significant association exists between polymorphisms at Nrf2 rs6721961 and Keap1 rs1048290 and the occurrence of lower extremity atherosclerosis in elderly individuals; however, Nrf2 rs35652124 is not significantly associated. 2. Clinical sequencing of the Nrf2 gene combined with relevant clinical indicators and predictive modeling can aid in early clinical intervention for LEAD in elderly populations.