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

Abstract

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-α (TNF-α) 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-α 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-α −238G→A and −308G→A polymorphisms.Results:PUFA intake was positively associated with serum HDL cholesterol in carriers of the −238A allele (β = 0.06 ± 0.03 mmol/L per 1% of energy from PUFAs; P = 0.03), but negatively associated in those with the −238GG genotype (β = −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 (β = −0.07 ± 0.02, P = 0.002), but not in those with the −308GG genotype (β = 0.02 ± 0.02, P = 0.13) (P = 0.001 for interaction). A stronger gene × 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-α 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.