title: Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil.
abstract: OBJECTIVE
  To investigate the impact of apolipoprotein E (apoE) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) intervention in humans.
  
  
  RESULTS
  38 healthy normolipidaemic males, prospectively recruited on the basis of apoE genotype (n=20 E3/E3 and n=18 E3/E4), completed a double-blind placebo-controlled cross-over trial, consisting of 3 x 4 week intervention arms of either control oil, EPA-rich oil (ERO, 3.3g EPA/day) or DHA-rich oil (DRO, 3.7g DHA/day) in random order, separated by 10 week wash-out periods. A significant genotype-independent 28% and 19% reduction in plasma triglycerides in response to ERO and DRO was observed. For total cholesterol (TC), no significant treatment effects were evident; however a significant genotype by treatment interaction emerged (P=0.045), with a differential response to ERO and DRO in E4 carriers. Although the genotype x treatment interaction for LDL-cholesterol (P=0.089) did not reach significance, within DRO treatment analysis indicated a 10% increase in LDL (P=0.029) in E4 carriers with a non-significant 4% reduction in E3/E3 individuals. A genotype-independent increase in LDL mass was observed following DRO intervention (P=0.018). Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins (VLDL) from the human trial, indicated that following DRO treatment, VLDL(2) fractions obtained from E3/E4 individuals resulted in a significant 32% (P=0.002) reduction in LDL uptake relative to the control.
  
  
  CONCLUSIONS
  High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers, which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup.
authors.affiliation: Hugh Sinclair Unit of Nutrition, School of Chemistry, Food Biosciences and Pharmacy, University of Reading, Reading, UK.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Olano-Martin
authors.forename: Eliz
authors.initials: E
authors.lastname: Anil
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Packard
authors.forename: Dorothy
authors.initials: D
authors.lastname: Bedford
authors.forename: Grace
authors.initials: G
authors.lastname: Stewart
authors.forename: Dammika
authors.initials: D
authors.lastname: Peiris
authors.forename: Christine M
authors.initials: CM
authors.lastname: Williams
authors.forename: Anne M
authors.initials: AM
authors.lastname: Minihane
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D002460:Cell Line; D008078:Cholesterol, LDL / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D005395:Fish Oils; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid