NF-κB −94Ins/Del ATTG polymorphism modifies the association between dietary polyunsaturated fatty acids and HDL-cholesterol in two distinct populations

Abstract

We previously showed that polymorphisms in the tumor necrosis factor (TNF)-α gene, which is regulated by nuclear factor kappa B (NF-κB), modify the association between dietary polyunsaturated fatty acid (PUFA) intake and circulating HDL-cholesterol. Our objective was to determine whether a common polymorphism in the NFKB1 gene (−94Ins/Del ATTG) interacts with PUFA intake to affect HDL-cholesterol in two distinct populations. Participants were diabetes-free young adults ( n = 593) and older individuals with diet-treated type 2 diabetes ( n = 103). The NF-κB polymorphism modified the association between dietary PUFA intake and HDL-cholesterol in both populations ( p = 0.02 and 0.005 for interaction). Among individuals with the Ins/Ins genotype, each 1% increase in energy from PUFA was associated with a 0.03 ± 0.01 mmol/L ( p for slope = 0.009) and 0.06 ± 0.02 mmol/L ( p = 0.02) increase in HDL-cholesterol among participants from the diabetes-free and diabetic populations. An inverse relationship was observed among those with the Del/Del genotype, which was significantly different from that of the Ins/Ins groups in both populations ( p = 0.02 and 0.006). No effects were observed for the Ins/Del genotype in either population ( p > 0.05). These findings show that this functional polymorphism in the NF-kB gene modifies the association between PUFA intake and plasma HDL-cholesterol in two distinct populations.