polymorphism and susceptibility to ischemic stroke in a Chinese population.

Background: Ischemic stroke (IS) is a major health concern in the Chinese population. Previous studies have highlighted the role of NRF2 in IS. This study investigates the association between NRF2 polymorphisms and IS susceptibility in a Chinese population.

Methods: This retrospective study included Chinese patients diagnosed with IS based on clinical symptoms, neurological examinations, and brain imaging findings from computed tomography or magnetic resonance imaging. Age- and sex-matched unrelated individuals with no family history of stroke, tumors, or genetic diseases served as controls. Peripheral blood samples were collected to genotype seven single-nucleotide polymorphisms (SNPs) in NRF2 (rs13005431, rs4893819, rs6721961, rs35652124, rs6726395, rs2364723, rs2706110) using the SNaPshot method. Binary logistic regression analysis was used to assess associations between these SNPs and IS risk. NRF2 and reactive oxygen species (ROS) levels in peripheral blood were measured. The relationship between rs35652124 and NRF2 expression was evaluated using expression quantitative trait locus (eQTL) analysis.

Results: All seven NRF2 SNPs conformed to Hardy-Weinberg equilibrium. Six SNPs (rs13005431, rs4893819, rs6721961, rs6726395, rs2364723, and rs2706110) showed no significant differences in distribution between the case and control groups ( > 0.05). However, the TC genotype of rs35652124 in the co-dominant model was significantly associated with increased IS risk. The distribution of this genotype aligned with trends observed in East Asia and the Chinese Han population but varied across other global populations. The CCTTGGC haplotype was the most common in both groups. Stratified analysis of rs35652124 showed no association with confounding factors such as age, sex, hypertension, diabetes, or lipid levels. NRF2 and ROS levels were higher in IS patients than in controls, but did not differ by rs35652124 genotype. Concurrently, eQTL analysis indicated that rs35652124 did not affect NRF2 expression in peripheral blood.

Conclusion: The NRF2 rs35652124 polymorphism is associated with IS susceptibility, suggesting it may be a potential genetic risk factor for IS.