title: Glu298Asp polymorphism influences the beneficial effects of fish oil fatty acids on postprandial vascular function.
abstract: Our objective was to determine whether the endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism influences vascular response to raised NEFA enriched with saturated fatty acids (SFA) or long-chain (LC) n-3 polyunsaturated fatty acids (PUFA). Subjects were prospectively recruited for genotype (Glu298, n = 30 and Asp298, n = 29; balanced for age and gender) consumed SFA on two occasions, with and without the substitution of 0.07 g fat/kg body weight with LC n-3 PUFA, and with heparin infusion to elevate NEFA. Endothelial function was measured before and after NEFA elevation (240 min), with blood samples taken every 30 min. Flow-mediated dilation (FMD) decreased following SFA alone and increased following SFA+LC n-3 PUFA. There were 2-fold differences in the change in FMD response to the different fat loads between the Asp298 and Glu298 genotypes (P = 0.002) and between genders (P < 0.02). Sodium nitroprusside-induced reactivity, measured by laser Doppler imaging with iontophoresis, was significantly greater with SFA+LC n-3 PUFA in all female subjects (P < 0.001) but not in males. Elevated NEFA influences both endothelial-dependent and endothelial-independent vasodilation during the postprandial phase. Effects of fat composition appear to be genotype and gender dependent, with the greatest difference in vasodilatory response to the two fat loads seen in the Asp298 females.
authors: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, RG6 6AP, UK.
authors: Abby K
authors: AK
authors: Thompson
authors: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, RG6 6AP, UK.
authors: Katie J
authors: KJ
authors: Newens
authors: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, RG6 6AP, UK.
authors: Kim G
authors: KG
authors: Jackson
authors: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, RG6 6AP, UK.
authors: John
authors: J
authors: Wright
authors: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, RG6 6AP, UK. Electronic address: c.m.williams@reading.ac.uk.
authors: Christine M
authors: CM
authors: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005227:Fatty Acids / Q000008:administration & dosage* / Q000737:chemistry; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D011446:Prospective Studies; D016037:Single-Blind Method; D014664:Vasodilation / Q000187:drug effects* / Q000235:genetics
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D005395:Fish Oils; D052250:Nitric Oxide Synthase Type III