Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]

Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genet...

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Main Authors: Szilvia Bokor, Julie Dumont, Andre Spinneker, Marcela Gonzalez-Gross, Esther Nova, Kurt Widhalm, George Moschonis, Peter Stehle, Philippe Amouyel, Stefaan De Henauw, Dènes Molnàr, Luis A. Moreno, Aline Meirhaeghe, Jean Dallongeville
Format: Article
Language:English
Published: Elsevier 2010-08-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520370681
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author Szilvia Bokor
Julie Dumont
Andre Spinneker
Marcela Gonzalez-Gross
Esther Nova
Kurt Widhalm
George Moschonis
Peter Stehle
Philippe Amouyel
Stefaan De Henauw
Dènes Molnàr
Luis A. Moreno
Aline Meirhaeghe
Jean Dallongeville
author_facet Szilvia Bokor
Julie Dumont
Andre Spinneker
Marcela Gonzalez-Gross
Esther Nova
Kurt Widhalm
George Moschonis
Peter Stehle
Philippe Amouyel
Stefaan De Henauw
Dènes Molnàr
Luis A. Moreno
Aline Meirhaeghe
Jean Dallongeville
author_sort Szilvia Bokor
collection DOAJ
description Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean ± SD age: 14.7 ± 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18 ≤ P ≤ 6.1E-5), lower C20:4n-6 levels (7.1E-69 ≤ P ≤ 1.2E-12), and lower D5D activity (7.2E-44 ≤ P ≤ 4.4E-5). All haplotypes carrying the rs174546 minor allele were associated with lower D5D activity, suggesting that this SNP is in linkage disequilibrium with a functional SNP within FADS1. In contrast, only the rs968567 minor allele was associated with higher D6D activity (P = 1.5E-6). This finding agrees with an earlier in vitro study showing that the minor allele of rs968567 is associated with a higher FADS2 promoter activity. These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents.
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spelling doaj.art-8223ebddd1b74fc38edf903da4df39952022-12-21T18:54:55ZengElsevierJournal of Lipid Research0022-22752010-08-0151823252333Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]Szilvia Bokor0Julie Dumont1Andre Spinneker2Marcela Gonzalez-Gross3Esther Nova4Kurt Widhalm5George Moschonis6Peter Stehle7Philippe Amouyel8Stefaan De Henauw9Dènes Molnàr10Luis A. Moreno11Aline Meirhaeghe12Jean Dallongeville13Inserm U744; Institut Pasteur de Lille; Univ Lille Nord de France; UDSL; 59019 Lille, France; Institut für Ernährungs- und Lebensmittelwissenschaften-ErnährungphysiologieInserm U744; Institut Pasteur de Lille; Univ Lille Nord de France; UDSL; 59019 Lille, France; Institut für Ernährungs- und Lebensmittelwissenschaften-Ernährungphysiologie53115 Bonn, Germany; Department of Health and Human PerformanceFaculty of Physical Activity and Sport Sciences- INEF, Universidad Politécnica de Madrid, Madrid, Spain; Department of Metabolism and NutritionInstituto del Frío-ICTAN, CSIC 10 28040 Madrid, Spain; Department of PediatricsDivision of Clinical Nutrition and Prevention, Medical University of Vienna, 1090 Vienna, Austria; Department of Nutrition and DieteticsHarokopio University, Athens, Greece; Department of Public Health53115 Bonn, Germany; Department of Health and Human PerformanceInserm U744; Institut Pasteur de Lille; Univ Lille Nord de France; UDSL; 59019 Lille, France; Institut für Ernährungs- und Lebensmittelwissenschaften-ErnährungphysiologieFaculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium; Department of PaediatricsUniversity of Pècs, 7623 Pècs, Hungary; and GENUD Research GroupEscuela Universitaria de Ciencias de la Salud, Universidad de Zaragoza, 50009 Zaragoza, SpainInserm U744; Institut Pasteur de Lille; Univ Lille Nord de France; UDSL; 59019 Lille, France; Institut für Ernährungs- und Lebensmittelwissenschaften-ErnährungphysiologieTo whom correspondence should be addressed; Inserm U744; Institut Pasteur de Lille; Univ Lille Nord de France; UDSL; 59019 Lille, France; Institut für Ernährungs- und Lebensmittelwissenschaften-ErnährungphysiologieGenetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean ± SD age: 14.7 ± 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18 ≤ P ≤ 6.1E-5), lower C20:4n-6 levels (7.1E-69 ≤ P ≤ 1.2E-12), and lower D5D activity (7.2E-44 ≤ P ≤ 4.4E-5). All haplotypes carrying the rs174546 minor allele were associated with lower D5D activity, suggesting that this SNP is in linkage disequilibrium with a functional SNP within FADS1. In contrast, only the rs968567 minor allele was associated with higher D6D activity (P = 1.5E-6). This finding agrees with an earlier in vitro study showing that the minor allele of rs968567 is associated with a higher FADS2 promoter activity. These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents.http://www.sciencedirect.com/science/article/pii/S0022227520370681geneticsadolescentslipoproteinstriglyceridearachidonic acid
spellingShingle Szilvia Bokor
Julie Dumont
Andre Spinneker
Marcela Gonzalez-Gross
Esther Nova
Kurt Widhalm
George Moschonis
Peter Stehle
Philippe Amouyel
Stefaan De Henauw
Dènes Molnàr
Luis A. Moreno
Aline Meirhaeghe
Jean Dallongeville
Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]
Journal of Lipid Research
genetics
adolescents
lipoproteins
triglyceride
arachidonic acid
title Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]
title_full Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]
title_fullStr Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]
title_full_unstemmed Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]
title_short Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]
title_sort single nucleotide polymorphisms in the fads gene cluster are associated with delta 5 and delta 6 desaturase activities estimated by serum fatty acid ratios s
topic genetics
adolescents
lipoproteins
triglyceride
arachidonic acid
url http://www.sciencedirect.com/science/article/pii/S0022227520370681
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