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dc.contributor.authorSorli, Jose V
dc.contributor.authorAsensio, Eva M
dc.contributor.authorBarragan, Rocio
dc.contributor.authorGonzalez, Jose I
dc.contributor.authorGimenez-Alba, Ignacio M
dc.contributor.authorZanon-Moreno, Vicente
dc.contributor.authorEstruch, Ramon
dc.contributor.authorRamirez-Sabio, Judith B
dc.contributor.authorPascual, Eva C
dc.contributor.authorOrtega-Azorin, Carolina
dc.contributor.authorOrdovas, Jose M 
dc.contributor.authorCorella, Dolores
dc.date.accessioned2021-06-22T06:44:27Z
dc.date.available2021-06-22T06:44:27Z
dc.date.issued2020-01-24
dc.identifier.citationNutrients. 2020; 12(2):310es_ES
dc.identifier.issn2072-6643es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13170
dc.description.abstractMany early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (FADS) gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GWAS) have been carried out in other populations and none of them have investigated sex and Mediterranean dietary pattern interactions at the genome-wide level. Our aims were to undertake a GWAS to discover the genes most associated with serum PUFA concentrations (omega-3, omega-6, and some fatty acids) in a scarcely studied Mediterranean population with metabolic syndrome, and to explore sex and adherence to Mediterranean diet (MedDiet) interactions at the genome-wide level. Serum PUFA were determined by NMR spectroscopy. We found strong robust associations between various SNPs in the FADS cluster and omega-3 concentrations (top-ranked in the adjusted model: FADS1-rs174547, p = 3.34 × 10-14; FADS1-rs174550, p = 5.35 × 10-14; FADS2-rs1535, p = 5.85 × 10-14; FADS1-rs174546, p = 6.72 × 10-14; FADS2-rs174546, p = 9.75 × 10-14; FADS2- rs174576, p = 1.17 × 10-13; FADS2-rs174577, p = 1.12 × 10-12, among others). We also detected a genome-wide significant association with other genes in chromosome 11: MYRF (myelin regulatory factor)-rs174535, p = 1.49 × 10-12; TMEM258 (transmembrane protein 258)-rs102275, p = 2.43 × 10-12; FEN1 (flap structure-specific endonuclease 1)-rs174538, p = 1.96 × 10-11). Similar genome-wide statistically significant results were found for docosahexaenoic fatty acid (DHA). However, no such associations were detected for omega-6 PUFAs or linoleic acid (LA). For total PUFA, we observed a consistent gene*sex interaction with the DNTTIP2 (deoxynucleotidyl transferase terminal interacting protein 2)-rs3747965 p = 1.36 × 10-8. For adherence to MedDiet, we obtained a relevant interaction with the ME1 (malic enzyme 1) gene (a gene strongly regulated by fat) in determining serum omega-3. The top-ranked SNP for this interaction was ME1-rs3798890 (p = 2.15 × 10-7). In the regional-wide association study, specifically focused on the FADS1/FASD2/FADS3 and ELOVL (fatty acid elongase) 2/ELOVL 5 regions, we detected several statistically significant associations at p < 0.05. In conclusion, our results confirm a robust role of the FADS cluster on serum PUFA in this population, but the associations vary depending on the PUFA. Moreover, the detection of some sex and diet interactions underlines the need for these associations/interactions to be studied in all specific populations so as to better understand the complex metabolism of PUFA.es_ES
dc.description.sponsorshipThis study was partially funded, by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) (grants CIBER 06/03, PI06/1326, PI13/00728, PI16/00366, SAF2016–80532-R and FPU 18/01703); the University Jaume I (grants P1–1B2013–54 and COGRUP/2016/06); the Rei Jaume I Award for Medical Research 2018; the Fundació La Marató de TV3 (grant 538/U/2016); and the Generalitat Valenciana (grants PROMETEO2017/017, AEST/2018/044 and APOSTD/2019/136) and the US Department of Agriculture, Agriculture Research Service (grant 8050–51000--098--00D).es_ES
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshDiet, Mediterranean es_ES
dc.subject.meshPolymorphism, Single Nucleotide es_ES
dc.subject.meshAged es_ES
dc.subject.meshClinical Trials as Topic es_ES
dc.subject.meshCross-Sectional Studies es_ES
dc.subject.meshFatty Acid Desaturases es_ES
dc.subject.meshFatty Acid Elongases es_ES
dc.subject.meshFatty Acids, Omega-3 es_ES
dc.subject.meshFatty Acids, Omega-6 es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGene-Environment Interaction es_ES
dc.subject.meshGenetic Predisposition to Disease es_ES
dc.subject.meshGenome-Wide Association Study es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMetabolic Syndrome es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshPhenotype es_ES
dc.subject.meshRisk Factors es_ES
dc.subject.meshSex Factors es_ES
dc.subject.meshSpain es_ES
dc.subject.meshTreatment Outcome es_ES
dc.titleGenome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID31991592es_ES
dc.format.volume12es_ES
dc.format.number2es_ES
dc.format.page310es_ES
dc.identifier.doi10.3390/nu12020310es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderJaume I University (España) 
dc.contributor.funderFundación La Marató TV3 
dc.contributor.funderGeneralitat Valenciana (España) 
dc.contributor.funderUnited States Department of Agriculture 
dc.description.peerreviewedNoes_ES
dc.relation.publisherversionhttps://doi.org/10.3390/nu12020310es_ES
dc.identifier.journalNutrientses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionaleses_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CIBER 06/03es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI06/1326es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI13/00728es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16/00366es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016–80532-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU 18/01703es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/P1–1B2013–54es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/COGRUP/2016/06es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/538/U/2016es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PROMETEO2017/017es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/AEST/2018/044es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/APOSTD/2019/136es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
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