Genetic Polymorphisms of Tumor Necrosis Factor-Alpha Modify the Association between Dietary Polyunsaturated Fatty Acids and Plasma High-Density Lipoprotein-Cholesterol Concentrations in a Population of Young Adults

Abstract

Background/Aims: Genetic polymorphisms in tumor necrosis factor-α (TNF-α) modify the association between polyunsaturated fatty acids (PUFA) and plasma high-density lipoprotein (HDL) cholesterol in a population with type 2 diabetes. The objective of this study was to determine whether this gene × diet interaction is observed in a diabetes-free population and whether it is due to n–3 or n–6 PUFA. Methods: Subjects (n = 595) were aged 20–29 years and genotyped for the TNF-α –238G>A and TNF-α –308G>A polymorphisms. Diet was assessed using a food frequency questionnaire. Subjects were grouped as having no minor A allele at both the –238 and –308 positions (0/0), or one minor A allele at either the –238 (1/0) or the –308 (0/1) position. Results: TNF-α genotypes modified the association between dietary PUFA and HDL-cholesterol concentrations (p = 0.04 for interaction). Among individuals with the 0/0 genotype, total PUFA was positively associated with HDL-cholesterol in both men (p = 0.008) and women (p = 0.03), and for both n–6 (p = 0.004) and n–3 (p = 0.04) PUFA. However, an inverse relationship was observed among men carrying the 1/0 genotype (p = 0.005). Conclusion: These findings demonstrate that TNF-α genotypes modify the association between dietary PUFA and HDL-cholesterol and provide further evidence that inflammation is involved in the reverse cholesterol transport.