title: Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro.
abstract: BACKGROUND
  Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. We have previously shown that HDL does not protect LDL from oxidation in vitro, but is in fact oxidized fastest of all lipoproteins due to its rich polyunsaturated fatty acid (PUFA) composition, which is oxidation promoting. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA status. There is a deletion [T/-] in the promoter region of the Δ6 -desaturase gene (FADS2, rs 3834458), which has a direct inhibitory influence on production of PUFA from linoleic and alpha-linolenic acid. To investigate the possible role of rs 3834458 in lipoprotein modification, oxidation of LDL with HDL₂ or HDL₃ were analyzed from plasma of 58 free-living individuals.
  
  
  RESULTS
  Total eicosapentaenoic acid and arachidonic acid were significantly decreased in plasma from the 10 subjects homozygous for the deletion in FADS2 rs 3834458. When the isolated LDL and HDL₂ were subjected to Cu²⁺-induced oxidation, these subjects showed decreased rate of appearance (p = 0.027) and the final concentration of conjugated dienes (p = 0.033) compared to the other genotypes. For oxidation of LDL with HDL₃, the final concentration of conjugated dienes was also significantly decreased in subjects with [-/-] compared with [T/T] and [T/-] (p = 0.034).
  
  
  CONCLUSIONS
  We conclude that FADS2 genotype may play a role in peroxidation susceptibility of lipoproteins.
authors.affiliation: Department of Medical Biochemistry, University of Tampere Medical School, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Solakivi
authors.forename: Tarja
authors.initials: T
authors.lastname: Kunnas
authors.forename: Olli
authors.initials: O
authors.lastname: Jaakkola
authors.forename: Jaana
authors.initials: J
authors.lastname: Renko
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Seppo T
authors.initials: ST
authors.lastname: Nikkari
mesh_terms: D016718:Arachidonic Acid / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D050602:Linoleoyl-CoA Desaturase / Q000235:genetics*; D015227:Lipid Peroxidation / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000235:genetics; D010084:Oxidation-Reduction; D017384:Sequence Deletion
chemical_list: D005231:Fatty Acids, Unsaturated; D008077:Lipoproteins, LDL; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D050602:Linoleoyl-CoA Desaturase