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.

OBJECTIVE

Genetic polymorphisms in tumor necrosis factor-alpha (TNF-alpha) 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 x 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-alpha -238G>A and TNF-alpha -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-alpha 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).

CONCLUSIONS

These findings demonstrate that TNF-alpha genotypes modify the association between dietary PUFA and HDL-cholesterol and provide further evidence that inflammation is involved in the reverse cholesterol transport.