Genetic polymorphisms of tumor necrosis factor-alpha modify the association between dietary polyunsaturated fatty acids and fasting HDL-cholesterol and apo A-I concentrations.

Background: Heterogeneity in circulating lipid concentrations in response to dietary polyunsaturated fatty acids (PUFAs) may be due, in part, to genetic variations. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that can induce hyperlipidemia and is known to be modulated by dietary PUFAs.

Objective: The objective was to determine whether TNF-alpha genotypes modify the association between dietary PUFA intake and serum lipid concentrations.

Design: The study involved 53 men and 56 women aged 42-75 y with type 2 diabetes. Dietary intakes were assessed with the use of a 3-d food record, and blood samples were collected to determine fasting serum lipids. DNA was isolated from blood for genotyping by polymerase chain reaction-restriction fragment length polymorphism for the TNF-alpha -238G-->A and -308G-->A polymorphisms.

Results: PUFA intake was positively associated with serum HDL cholesterol in carriers of the -238A allele (beta = 0.06 +/- 0.03 mmol/L per 1% of energy from PUFAs; P = 0.03), but negatively associated in those with the -238GG genotype (beta = -0.03 +/- 0.01, P = 0.03) (P = 0.004 for interaction). PUFA intake was inversely associated with HDL cholesterol in carriers of the -308A allele (beta = -0.07 +/- 0.02, P = 0.002), but not in those with the -308GG genotype (beta = 0.02 +/- 0.02, P = 0.13) (P = 0.001 for interaction). A stronger gene x diet interaction was observed when the polymorphisms at the 2 positions (-238/-308) were combined (P = 0.0003). Similar effects were observed for apolipoprotein A-I, but not with other dietary fatty acids and serum lipids.

Conclusion: TNF-alpha genotypes modify the relation between dietary PUFA intake and HDL-cholesterol concentrations. These findings suggest that genetic variations affecting inflammation may explain some of the inconsistencies between previous studies relating PUFA intake and circulating HDL.