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Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW 2042, Australia.ORCID iD: 0000-0002-3320-796X
Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.ORCID iD: 0000-0003-2256-6972
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2018 (English)In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 11, article id 1791Article in journal (Refereed) Published
Abstract [en]

Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of delta-5-desaturase (D5D), delta-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters (n = 1453) and adipose tissue (n = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp (n = 554). Variants at the FADS1 were strongly associated with D5D in both cholesterol esters (p = 1.9 x 10(-70)) and adipose tissue (p = 1.1 x 10(-27)). Variants in three further loci were associated with D6D in cholesterol esters (FADS2, p = 3.0 x 10(-67); PDXDCI, p = 4.8 x 10(-8); and near MC4R, p = 3.7 x 10(-8)) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (PKDL1, p = 2.2 x 10(-19)). Genetic variants near MC4R were associated with IS (p = 3.8 x 10(-3)). The FADS cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS.

Place, publisher, year, edition, pages
2018. Vol. 10, no 11, article id 1791
Keywords [en]
fatty acid, desaturase, Genome-wide association study (GWAS), Insulin sensitivity, adipose tissue, cholesterol ester
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:uu:diva-372460DOI: 10.3390/nu10111791ISI: 000451547700229PubMedID: 30453627OAI: oai:DiVA.org:uu-372460DiVA, id: diva2:1276034
Funder
Swedish Research Council, 2007-2135Forte, Swedish Research Council for Health, Working Life and Welfare, 2013-01586Swedish Foundation for Strategic Research Swedish Heart Lung Foundation, 20070212The Royal Swedish Academy of SciencesSwedish Diabetes AssociationSwedish Society of MedicineNovo NordiskThe Karolinska Institutet's Research FoundationEU, FP7, Seventh Framework Programme, FP7/2007-2013Swedish National Infrastructure for Computing (SNIC), p2013055Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved

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