HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fontaine-Bisson, B. Articles by El-Sohemy, A. Search for Related Content PubMed PubMed Citation Articles by Fontaine-Bisson, B. Articles by El-Sohemy, A. Agricola Articles by Fontaine-Bisson, B. Articles by El-Sohemy, A.

Genetic polymorphisms of tumor necrosis factor- modify the association between dietary polyunsaturated fatty acids and fasting HDL-cholesterol and apo A-I concentrations^1,2,3

¹ From the Department of Nutritional Sciences (BF-B, TMSW, RGJ, LAL, and AE-S), the Departments of Laboratory Medicine and Pathobiology and Medicine (PWC), and the Department of Public Health Sciences (PNC), University of Toronto, Toronto, Canada; the Departments of Medicine (JLC) and Nutrition (RRL), Université de Montréal and Research Center, Centre Hospitalier de l'Université de Montréal, Montreal, Canada; the Department of Medicine, Division of Endocrinology and Metabolism, Université de Sherbrooke, Sherbrooke, Canada (PM); St Michael's Hospital, Toronto, Toronto, Canada (TMSW, RGJ, and LAL); St Joseph's Health Centre, London, Canada (NWR); the Heritage Medical Research Centre, Edmonton, Canada (EAR); and the Department of Medicine, St Michael's Hospital, Toronto, Toronto, Canada (PWC)

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- (TNF-) 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- 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- –238GA and –308GA polymorphisms.

Results:PUFA intake was positively associated with serum HDL cholesterol in carriers of the –238A allele (ß = 0.06 ± 0.03 mmol/L per 1% of energy from PUFAs; P = 0.03), but negatively associated in those with the –238GG genotype (ß = –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 (ß = –0.07 ± 0.02, P = 0.002), but not in those with the –308GG genotype (ß = 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- 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.

Key Words: Tumor necrosis factor- • genotype • polyunsaturated fatty acids • HDL cholesterol • apolipoprotein A-I • type 2 diabetes