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Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro

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 a...

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Autores principales: Solakivi, Tiina, Kunnas, Tarja, Jaakkola, Olli, Renko, Jaana, Lehtimäki, Terho, Nikkari, Seppo T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680190/
https://www.ncbi.nlm.nih.gov/pubmed/23721366
http://dx.doi.org/10.1186/1476-511X-12-80
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author Solakivi, Tiina
Kunnas, Tarja
Jaakkola, Olli
Renko, Jaana
Lehtimäki, Terho
Nikkari, Seppo T
author_facet Solakivi, Tiina
Kunnas, Tarja
Jaakkola, Olli
Renko, Jaana
Lehtimäki, Terho
Nikkari, Seppo T
author_sort Solakivi, Tiina
collection PubMed
description 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 Δ(6) –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 HDL(2) or HDL(3) 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 HDL(2) were subjected to Cu(2+)-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 HDL(3), the final concentration of conjugated dienes was also significantly decreased in subjects with [−/−] compared with [T/T] and [T/-] (p = 0.034). CONCLUSION: We conclude that FADS2 genotype may play a role in peroxidation susceptibility of lipoproteins.
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spelling pubmed-36801902013-06-13 Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro Solakivi, Tiina Kunnas, Tarja Jaakkola, Olli Renko, Jaana Lehtimäki, Terho Nikkari, Seppo T Lipids Health Dis Research 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 Δ(6) –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 HDL(2) or HDL(3) 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 HDL(2) were subjected to Cu(2+)-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 HDL(3), the final concentration of conjugated dienes was also significantly decreased in subjects with [−/−] compared with [T/T] and [T/-] (p = 0.034). CONCLUSION: We conclude that FADS2 genotype may play a role in peroxidation susceptibility of lipoproteins. BioMed Central 2013-05-30 /pmc/articles/PMC3680190/ /pubmed/23721366 http://dx.doi.org/10.1186/1476-511X-12-80 Text en Copyright © 2013 Solakivi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Solakivi, Tiina
Kunnas, Tarja
Jaakkola, Olli
Renko, Jaana
Lehtimäki, Terho
Nikkari, Seppo T
Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro
title Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro
title_full Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro
title_fullStr Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro
title_full_unstemmed Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro
title_short Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro
title_sort delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680190/
https://www.ncbi.nlm.nih.gov/pubmed/23721366
http://dx.doi.org/10.1186/1476-511X-12-80
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