NRF2 Genetic Polymorphism Modifies the Association of Plasma Selenium Levels With Incident Coronary Heart Disease among Type 2 Diabetes Individuals

Existing studies found that both plasma selenium and NRF2 promoter variants (e.g., rs6721961) were associated with cardiovascular disease risk in the general population. However, epidemiological evidence on the interaction between plasma selenium and NRF2 genetic susceptibility in relation to incident coronary heart disease (CHD) risk remains scarce, especially among individuals with type 2 diabetes (T2D). Thus, we examined whether rs6721961 in the NRF2 gene might modify the association between plasma selenium levels and incident CHD risk among T2D. During a mean (SD) follow-up period of 6.90 (2.96) years, 798 incident CHD cases were identified in 2,251 T2D cases. Risk allele carriers (GT/TT) of rs6721961 showed a higher risk of incident CHD among T2D (adjusted HR = 1.17, 95% CI: 1.02–1.35) vs. non-risk allele carriers (GG). Each 22.8 μg/L increase in plasma selenium levels was associated with a reduced risk of incident CHD among T2D with risk allele (GT/TT; HR = 0.80, 95% CI: 0.71–0.89), whereas no association was found in those with non-risk allele (GG; Pinteraction = 0.004), indicating that NRF2 promoter polymorphism might modify the association between plasma selenium levels and incident CHD risk among T2D. Our study suggests that redox-related genetic variants should be considered to identify populations that might benefit most from selenium supplementation. Further mechanistic studies are warranted.