FADS Polymorphisms Affect the Clinical and Biochemical Phenotypes of Metabolic Syndrome

. 2022 Jun 20 ; 12 (6) : . [epub] 20220620

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid35736500

Grantová podpora
MH CZ DRO-VFN64165 the Ministry of Health of the Czech Republic
"Cooperatio - Gastroenterology" the Charles University Research program

Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.

Zobrazit více v PubMed

Dizaji B.F. The investigations of genetic determinants of the metabolic syndrome. Diabetes Metab. Syndr. 2018;12:783–789. doi: 10.1016/j.dsx.2018.04.009. PubMed DOI

Zafar U., Khaliq S., Ahmad H.U., Manzoor S., Lone K.P. Metabolic syndrome: An update on diagnostic criteria, pathogenesis, and genetic links. Hormones. 2018;17:299–313. doi: 10.1007/s42000-018-0051-3. PubMed DOI

Fahed G., Aoun L., Bou Zerdan M., Allam S., Bou Zerdan M., Bouferraa Y., Assi H.I. Metabolic Syndrome: Updates on Pathophysiology and Management in 2021. Int. J. Mol. Sci. 2022;23:786. doi: 10.3390/ijms23020786. PubMed DOI PMC

Stančáková A., Laakso M. Genetics of metabolic syndrome. Rev. Endocr. Metab. Disord. 2014;15:243–252. doi: 10.1007/s11154-014-9293-9. PubMed DOI

Brown A.E., Walker M. Genetics of Insulin Resistance and the Metabolic Syndrome. Curr. Cardiol. Rep. 2016;18:75. doi: 10.1007/s11886-016-0755-4. PubMed DOI PMC

Panda C., Varadharaj S., Voruganti V.S. PUFA, genotypes and risk for cardiovascular disease. Prostaglandins Leukot. Essent. Fat. Acids. 2022;176:102377. doi: 10.1016/j.plefa.2021.102377. PubMed DOI

Das U.N. Metabolic Syndrome Pathophysiology: The Role of Essential Fatty Acids. 1st ed. Wiley-Blackwell; Ames, IA, USA: 2010. 268p

Vávrová L., Kodydková J., Zeman M., Dušejovská M., Macášek J., Staňková B., Tvrzická E., Žák A. Altered Activities of Antioxidant Enzymes in Patients with Metabolic Syndrome. Obes. Facts. 2013;6:39–47. doi: 10.1159/000348569. PubMed DOI PMC

Žák A., Burda M., Vecka M., Zeman M., Tvrzická E., Staňková B. Fatty Acid Composition Indicates Two Types of Metabolic Syndrome Independent of Clinical and Laboratory Parameters. Phys. Res. 2014;63:S375–S385. doi: 10.33549/physiolres.932868. PubMed DOI

Mayneris-Perxachs J., Guerendiain M., Castellote A.I., Estruch R., Covas M.I., Fitó M., Salas-Salvadó J., Martínez-González M.A., Aros F., Lamuela-Raventós R.M., et al. Plasma fatty acid composition, estimated desaturase activities, and their relation with the metabolic syndrome in a population at high risk of cardiovascular disease. Clin. Nutr. 2014;33:90–97. doi: 10.1016/j.clnu.2013.03.001. PubMed DOI

Zeman M., Vecka M., Burda M., Tvrzická E., Staňková B., Macášek J., Žák A. Phosphatidylcholine Determines Body Fat Parameters in Subjects with Metabolic Syndrome-Related Traits. Metabol. Syndrome Rel. Disord. 2017;15:371–378. doi: 10.1089/met.2017.0040. PubMed DOI

Muzsik A., Jeleń H.H., Chmurzynska A. Metabolic syndrome in postmenopausal women is associated with lower erythrocyte PUFA/MUFA and n-3/n-6 ratio: A case-control study. Prostaglandins Leukot. Essent. Fatty Acids. 2020;159:102155. doi: 10.1016/j.plefa.2020.102155. PubMed DOI

Lattka E., Illig T., Koletzko B., Heinrich J. Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism. Curr. Opin. Lipidol. 2010;21:64–69. doi: 10.1097/MOL.0b013e3283327ca8. PubMed DOI

Merino D.M., Johnston H., Clarke S., Roke K., Nielsen D., Badawi A., El-Sohemy A., Ma D.W., Mutch D.M. Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults. Mol. Genet. Metab. 2011;103:171–178. doi: 10.1016/j.ymgme.2011.02.012. PubMed DOI

Lattka E., Illig T., Heinrich J., Koletzko B. FADS Gene Cluster Polymorphisms: Important Modulators of Fatty Acid Levels and Their Impact on Atopic Diseases. J. Nutrigenet. Nutr. 2009;2:119–128. doi: 10.1159/000235559. PubMed DOI

Glaser C., Heinrich J., Koletzko B. Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism. Metabolism. 2010;59:993–999. doi: 10.1016/j.metabol.2009.10.022. PubMed DOI

Reynolds L.M., Dutta R., Seeds M.C., Kirsten N., Lake K.N., Hallmark B., Mathias R.A., Timothy D., Howard T.D., Chilton F.C. FADS genetic and metabolomic analyses identify the Δ5 desaturase (FADS1) step as a critical control point in the formation of biologically important lipids. Sci. Rep. 2020;10:15873. doi: 10.1038/s41598-020-71948-1. PubMed DOI PMC

Lankinen M., Uusitupa M., Schwab U. Genes and Dietary Fatty Acids in Regulation of Fatty Acid Composition of Plasma and Erythrocyte Membranes. Nutrients. 2018;10:1785. doi: 10.3390/nu10111785. PubMed DOI PMC

Nakamura M.T., Nara T.Y. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu. Rev. Nutr. 2004;24:345–376. doi: 10.1146/annurev.nutr.24.121803.063211. PubMed DOI

Lee J.M., Lee H., Kang S., Park W.J. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances. Nutrients. 2016;8:23. doi: 10.3390/nu8010023. PubMed DOI PMC

Lankinen M.A., Fauland A., Shimizu B.-I., Agren J., Wheelock C.E., Laakso M., Schwab U., Pihlajamaki J. Inflammatory response to dietary linoleic acid depends on FADS1 genotype. Am. J. Clin. Nutr. 2019;109:165–175. doi: 10.1093/ajcn/nqy287. PubMed DOI

Bokor S., Dumont J., Spinneker A., Gonzalez-Gross M., Nova E., Widhalm W., Moschonis G., Stehle P., Amouyel P., De Henauw S., et al. Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios. J. Lipid Res. 2010;51:2325–2333. doi: 10.1194/jlr.M006205. PubMed DOI PMC

Ameur A., Enroth S., Johansson A., Zaboli G., Igl W., Johansson A.C., Rivas M.A., Daly M.J., Schmitz G., Hicks A.A., et al. Genetic adaptation of fatty-acid metabolism: A human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids. Am. J. Hum. Genet. 2012;90:809–820. doi: 10.1016/j.ajhg.2012.03.014. PubMed DOI PMC

Malerba G., Schaeffer L., Xumerle L., Klopp N., Trabetti E., Biscuola M., Cavallari U., Galavotti R., Martinelli N., Guarini P., et al. SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids. 2008;43:289–299. doi: 10.1007/s11745-008-3158-5. PubMed DOI

Schaeffer L., Gohlke H., Müller M., Heid I.M., Palmer L.J., Kompauer I., Demmelmair H., Illig T., Koletzko B., Heinrich J. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum. Mol. Genet. 2006;15:1745–1756. doi: 10.1093/hmg/ddl117. PubMed DOI

Czumaj A., Sledzinski T. Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease. Nutrients. 2020;12:356. doi: 10.3390/nu12020356. PubMed DOI PMC

Brayner B., Kaur G., Keske M.A., Livingstone K.M. FADS Polymorphism, Omega-3 Fatty Acids and Diabetes Risk: A Systematic Review. Nutrients. 2018;10:758. doi: 10.3390/nu10060758. PubMed DOI PMC

Yang Q., Yin R.X., Cao X.L., Wu D.F., Chen W.X., Zhou Y.J. Association of two polymorphisms in the FADS1/FADS2 gene cluster and the risk of coronary artery disease and ischemic stroke. Int. J. Clin. Exp. Pathol. 2015;8:7318–7331. PubMed PMC

Kathiresan S., Willer C.J., Peloso G.M., Demissie S., Musunuru K., Schadt E.E., Kaplan L., Bennett D., Li Y., Tanaka T., et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat. Genet. 2009;41:56–65. doi: 10.1038/ng.291. PubMed DOI PMC

Nakayama K., Bayasgalan T., Tazoe F., Yanagisawa Y., Gotoh T., Yamanaka K., Ogawa A., Munkhtulga L., Chimedregze U., Kagawa Y., et al. A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle. Hum. Genet. 2010;127:685–690. doi: 10.1007/s00439-010-0815-6. PubMed DOI

Standl M., Lattka E., Stach B., Koletzko S., Bauer C.-P., von Berg A., Berdel D., Krämer U., Schaaf B., Röder S., et al. FADS1 FADS2 Gene Cluster, PUFA Intake and Blood Lipids in Children: Results from the GINIplus and LISAplus Studies. PLoS ONE. 2012;7:e37780. doi: 10.1371/journal.pone.0037780. PubMed DOI PMC

Park S., Kim D.S., Kang S. Carrying minor allele of FADS1 and haplotype of FADS1 and FADS2 increased the risk of metabolic syndrome and moderate but not low fat diets lowered the risk in two Korean cohorts. Eur. J. Nutr. 2019;58:831–842. doi: 10.1007/s00394-018-1719-9. PubMed DOI

Marklund M., Morris A.P., Mahajan A., Ingelsson E., Lindgren C.M., Lind L., Risérus U. Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity. Nutrients. 2018;10:1791. doi: 10.3390/nu10111791. PubMed DOI PMC

Ching Y.K., Chin Y.S., Appukutty M., Ramanchadran V., Yu C.Y., Ang G.Y., Gan W.Y., Chan Y.M., Teh L.K., Salleh M.Z. Interaction of Dietary Linoleic Acid and α-Linolenic Acids with rs174547 in FADS1 Gene on Metabolic Syndrome Components among Vegetarians. Nutrients. 2019;11:1686. doi: 10.3390/nu11071686. PubMed DOI PMC

Shetty S.S., Kumari N.S. Fatty acid desaturase 2 (FADS 2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus. Sci. Rep. 2021;11:13151. doi: 10.1038/s41598-021-92572-7. PubMed DOI PMC

Stančáková A., Paananen J., Soininen P., Kangas A.J., Bonnycastle L.L., Morken M.A., Collins F.S., Jackson A.U., Boehnke M.L., Kuusisto J., et al. Effects of 34 risk loci for type 2 diabetes or hyperglycemia on lipoprotein subclasses and their composition in 6,580 nondiabetic Finish men. Diabetes. 2011;60:1608–1616. doi: 10.2337/db10-1655. PubMed DOI PMC

Kwak J.H., Paik J.K., Kim O.Y., Jang Y., Lee S.H., Ordovas J.M., Lee J.H. FADS gene polymorphisms in Koreans: Association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease. Atherosclerosis. 2011;214:94–100. doi: 10.1016/j.atherosclerosis.2010.10.004. PubMed DOI

Roke K., Ralston J.C., Abdelmagid S., Nielsen D.E., Badawi A., El-Sohemy A., Ma D.W., Mutch D.M. Variation in the FADS1/2 gene cluster alters plasma n−6 PUFA and is weakly associated with hsCRP levels in healthy young adults. Prostaglandins Leukot. Essent. Fatty Acids. 2013;89:257–263. doi: 10.1016/j.plefa.2013.06.003. PubMed DOI

Vaittinen M., Walle P., Kuosmanen E., Männistö V., Käkelä P., Ågren J., Schwab U., Pihlajamäki J. FADS2 genotype regulates delta-6 desaturase aktivity and inflammation in human adipose tissue. J. Lipid Res. 2016;57:56–65. doi: 10.1194/jlr.M059113. PubMed DOI PMC

Rifkin S.B., Shrubsole M.J., Cai Q., Smalley W.E., Ness R.M., Swift L.L., Milne G., Zheng W., Murff H.J. Differences in erythrocyte phospholipid membrane long-chain polyunsaturated fatty acids and the prevalence of fatty acid desaturase genotype among African Americans and European Americans. Prostaglandins Leukot. Essent. Fatty Acids. 2021;164:102216. doi: 10.1016/j.plefa.2020.102216. PubMed DOI

Meuronen T., Lankinen M.A., Kärkkäinen O., Laakso M., Pihlajamäki J., Hanhineva K., Schwab U. FADS1 rs174550 genotype and high linoleic acid diet modify plasma PUFA phospholipids in a dietary intervention study. Eur. J. Nutr. 2022;61:1109–1120. doi: 10.1007/s00394-021-02722-w. PubMed DOI PMC

Hong S.H., Kwak J.H., Paik J.K., Chae J.S., Lee J.H. Association of polymorphisms in FADS gene with age-related changes in serum phospholipid polyunsaturated fatty acids and oxidative stress markers in middle-aged nonobese men. Clin. Interv. Aging. 2013;8:585–596. doi: 10.2147/CIA.S42096. PubMed DOI PMC

Kröger J., Schulze M.B. Recent insights into the relation of 5 desaturase and 6 desaturase activity to the development of type 2 diabetes. Curr. Opin. Lipidol. 2012;23:4–10. doi: 10.1097/MOL.0b013e32834d2dc5. PubMed DOI

Mansouri V., Javanmard S.H., Mahdavi M., Tajedini M.H. Association of Polymorphism in Fatty Acid Desaturase Gene with the Risk of Type 2 Diabetes in Iranian Population. Adv. Biomed. Res. 2018;7:98. doi: 10.4103/abr.abr_131_17. PubMed DOI PMC

Chen Y., Estampador A.C., Keller M., Poveda A., Dalla-Riva J., Johansson I., Renström F., Kurbasic A., Franks P.W., Varga T.V. The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden: The GLACIER Study. Int. J. Obes. 2019;43:808–820. doi: 10.1038/s41366-018-0112-3. PubMed DOI PMC

Dumont J., Goumidi L., Grenier-Boley B., Cottel D., Marecaux N., Montaye M., Wagner A., Arveiler D., Simon C., Ferrieres J., et al. Dietary linoleic acid interacts with FADS1 genetic variability to modulate HDL-Cholesterol and obesity-related traits. Clin. Nutr. 2018;37:1683–1689. doi: 10.1016/j.clnu.2017.07.012. PubMed DOI

Khamlaoui W., Mehri S., Hammami S., Hammouda S., Chraeif I., Elosua R., Hammami M. Association Between Genetic Variants in FADS1-FADS2 and ELOVL2 and Obesity, Lipid Traits, and Fatty Acids in Tunisian Population. Clin. Appl. Thromb. Hemost. 2020;26:1–9. doi: 10.1177/1076029620915286. PubMed DOI PMC

Maguolo A., Zusi C., Giontella A., Miraglia Del Giudice E., Tagetti A., Fava C., Morandi A., Maffeis C. Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity. Int. J. Obes. 2021;45:56–65. doi: 10.1038/s41366-020-00662-9. PubMed DOI

Metelcová T., Vaňková M., Zamrazilová H., Hovhannisyan M., Staňková B., Tvrzická E., Hill M., Hainer V., Včelák J., Kunešová M. FADS1 gene polymorphism(s) and fatty acid composition of serum lipids in adolescents. Lipids. 2021;56:499–508. doi: 10.1002/lipd.12317. PubMed DOI

de la Garza Puentes A., Montes Goyanes R., Chisaguano Tonato A.M., Torres-Espínola F.J., Arias García M., de Almeida L., Bonilla Aguirre M., Guerendiain M., Castellote Bargalló A.I., Segura Moreno M., et al. Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels- The PREOBE follow-up. PLoS ONE. 2017;12:e0179135. doi: 10.1371/journal.pone.0179135. PubMed DOI PMC

Song Z., Cao H., Qin L., Jiang Y. A Case-Control Study between Gene Polymorphisms of Polyunsaturated Fatty Acid Metabolic Rate-Limiting Enzymes and Acute Coronary Syndrome in Chinese Han Population. Biomed. Res. Int. 2013;2013:928178. doi: 10.1155/2013/928178. PubMed DOI PMC

Li S.-W., Wang J., Yang Y., Liu Z.-J., Cheng L., Liu H.-Y., Ma P., Wan Luo W., Liu S.-M. Polymorphisms in FADS1 and FADS2 alterplasma fatty acids and desaturase levels in type 2 diabetic patients with coronary artery disease. J. Transl. Med. 2016;14:79. doi: 10.1186/s12967-016-0834-8. PubMed DOI PMC

Yuan S., Bäck M., Bruzelius M., Mason A.M., Burgess S., Larsson S. Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases: A Mendelian Randomisation Study. Nutrients. 2019;11:3001. doi: 10.3390/nu11123001. PubMed DOI PMC

Sergeant S., Hugenschmidt C.E., Rudock M.E., Ziegler J.T., Ivester P., Ainsworth H.C., Vaidya D., Case L.D., Langefeld C.D., Freedman B.I., et al. Differences in Arachidonic Acid Levels and Fatty Acid Desaturase (FADS) Gene Variants in African Americans and European Americans with Diabetes/Metabolic Syndrome. Br. J. Nutr. 2012;107:547–555. doi: 10.1017/S0007114511003230. PubMed DOI PMC

Truong H., DiBello J.R., Ruiz-Narvaez E., Kraft P., Campos H., Baylin A. Does genetic variation in the D6-desaturase promoter modify the association between a-linolenic acid and the prevalence of metabolic syndrome? Am. J. Clin. Nutr. 2009;89:920–925. doi: 10.3945/ajcn.2008.27107. PubMed DOI PMC

Martinelli N., Girelli D., Malerba G., Guarini P., Illig T., Trabetti E., Sandri M., Friso S., Pizzolo F., Schaeffer L., et al. FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. Am. J. Clin. Nutr. 2008;88:941–949. doi: 10.1093/ajcn/88.4.941. PubMed DOI

Jump D.B. Fatty acid regulation of hepatic lipid metabolism. Curr. Opin. Clin. Nutr. Metab. Care. 2011;14:115–120. doi: 10.1097/MCO.0b013e328342991c. PubMed DOI PMC

Tosi F., Sartori F., Guarini P., Olivieri O., Martinelli N. Delta-5 and delta-6 desaturases: Crucial enzymes in polyunsaturated fatty acid-related pathways with pleiotropic influences in health and disease. Adv. Exp. Med. Biol. 2014;824:61–81. doi: 10.1007/978-3-319-07320-0_7. PubMed DOI

Kremmyda L.S., Tvrzická E., Staňková B., Žák A. Fatty acids as biocompounds: Their role in human metabolism, health and disease: A review. Part 2: Fatty acid physiological roles and applications in human health and disease. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2011;155:195–218. doi: 10.5507/bp.2011.052. PubMed DOI

Tintle N.L., Pottala J.V., Lacey S., Ramachandran V., Westra J., Rogers A., Clark J., Olthoff B., Larson M., Harris W., et al. A genome-wide association study of saturated, mono- and polyunsaturated red blood cell fatty acids in the Framingham heart offspring study. Prostaglandins Leukot. Essent. Fatty Acids. 2015;94:65–72. doi: 10.1016/j.plefa.2014.11.007. PubMed DOI PMC

Tvrzická E., Kremmyda L.S., Staňková B., Žák A. Fatty acids as biocompounds: Their role in human metabolism, health and disease--a review. Part 1: Classification, dietary sources and biological functions. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2011;155:117–130. doi: 10.5507/bp.2011.038. PubMed DOI

Solinas G., Borén J., Dulloo A.G. De novo lipogenesis in metabolic homeostasis: More friend than foe? Mol. Metab. 2015;4:367–377. doi: 10.1016/j.molmet.2015.03.004. PubMed DOI PMC

Saponaro C., Gaggini M., Carli F., Gastaldelli A. The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis. Nutrients. 2015;7:9453–9474. doi: 10.3390/nu7115475. PubMed DOI PMC

AlJohani A.M., Syed D.N., Ntambi J.M. Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism. Trends Endocrinol. Metab. 2017;28:831–842. doi: 10.1016/j.tem.2017.10.003. PubMed DOI PMC

Dron J.S., Hegele R.A. Genetics of Hypertriglyceridemia. Front. Endocrinol. 2020;11:455. doi: 10.3389/fendo.2020.00455. PubMed DOI PMC

Bauer R.C., Khetarpal S.A., Hand N.J., Rader D.J. Therapeutic targets of triglyceride metabolism as informed by human genetics. Trends Mol. Med. 2016;22:328–340. doi: 10.1016/j.molmed.2016.02.005. PubMed DOI

Žák A., Tvrzická E., Vecka M., Jáchymová M., Duffková L., Staňková B., Vávrová L., Kodydková J., Zeman M. Severity of metabolic syndrome unfavorably influences oxidative stress and fatty acid metabolism in men. Tohoku J. Exp. Med. 2007;212:359–371. doi: 10.1620/tjem.212.359. PubMed DOI

Ahotupa M., Ruutu M., Mantyla E. Simple methods of quantifying oxidation products and antioxidant potential of low density lipoproteins. Clin. Biochem. 1996;29:139–144. doi: 10.1016/0009-9120(95)02043-8. PubMed DOI

Esterbauer H., Gebicki J., Puhl H., Jürgens G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic. Biol. Med. 1992;13:341–390. doi: 10.1016/0891-5849(92)90181-F. PubMed DOI

Gromovsky A.D., Schugar R.C., Brown A.L., Helsley R.N., Burrows A.C., Ferguson D., Zhang R., Sansbury B.E., Lee R.G., Morton R.E., et al. The Δ-5 Fatty Acid Desaturase FADS1 Impacts Metabolic Disease by Balancing Pro-Inflammatory and Pro-Resolving Lipid Mediators. Arterioscler. Thromb. Vasc. Biol. 2018;38:218–231. doi: 10.1161/ATVBAHA.117.309660. PubMed DOI PMC

Mazoochian L., Sadeghi H.M., Pourfarzam M. The effect of FADS2 gene rs174583 polymorphism on desaturase activities, fatty acid profile, insulin resistance, biochemical indices, and incidence of type 2 diabetes. J. Res. Med. Sci. 2018;23:47. doi: 10.4103/jrms.JRMS_961_17. PubMed DOI PMC

Zec M.M., Krga I., Stojković L., Živković M., Pokimica B., Stanković A., Glibetic M. Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight? Nutrients. 2021;13:296. doi: 10.3390/nu13020296. PubMed DOI PMC

Dumont J., Huybrechts I., Spinneker A., Gottrand F., Grammatikaki E., Bevilacqua N., Vyncke K., Widhalm K., Kafatos A., Molnar D., et al. FADS1 genetic variability interacts with dietary alpha-linolenic acid intake to affect serum Non-HDL-Cholesterol concentrations in European adolescents. J. Nutr. 2011;141:1247–1253. doi: 10.3945/jn.111.140392. PubMed DOI

Kawashima A., Sugawara S., Okita M., Akahane T., Fukui K., Hashiuchi M., Kataoka C., Tsukamoto I. Plasma fatty acid composition, estimated desaturase activities, and intakes of energy and nutrient in Japanese Men with Abdominal Obesity or Metabolic syndrome. J. Nutr. Sci. Vitaminol. 2009;55:400–406. doi: 10.3177/jnsv.55.400. PubMed DOI

GWAS Catalog. [(accessed on 8 May 2022)]. Available online: https://www.ebi.ac.uk/gwas/variants/rs174537.

He Z., Zhang R., Jiang F., Zhang H., Zhao A., Xu B., Jin L., Wang T., Jia W., Jia W., et al. FADS1-FADS2 genetic polymorphisms are associated with fatty acid metabolism through changes in DNA methylation and gene expression. Clin. Epigenetics. 2018;10:113. doi: 10.1186/s13148-018-0545-5. PubMed DOI PMC

Lottenberg A.M., da Silva Alfonso M., Lavrador M.S., Machado R.M., Nakandakare E.R. The role of dietary fatty acids in the pathology of metabolic syndrome. J. Nutr. Biochem. 2012;23:1027–1040. doi: 10.1016/j.jnutbio.2012.03.004. PubMed DOI

Alberti K.G., Zimmet P., Shaw J. Metabolic syndrome—A new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet. Med. 2006;23:469–480. doi: 10.1111/j.1464-5491.2006.01858.x. PubMed DOI

Vecka M., Dušejovská M., Staňková B., Rychlík I., Žák A. A Matched Case-Control Study of Noncholesterol Sterols and Fatty Acids in Chronic Hemodialysis Patients. Metabolites. 2021;11:774. doi: 10.3390/metabo11110774. PubMed DOI PMC

Matthews D.R., Hosker J.P., Rudenski A.S., Naylor B.A., Treacher D.F., Turner R.C. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419. doi: 10.1007/BF00280883. PubMed DOI

Ward J.H., Jr. Hierarchical Grouping to Optimize an Objective Function. J. Amer. Statist. Assoc. 1963;58:236–244. doi: 10.1080/01621459.1963.10500845. DOI

Phan L., Jin Y., Zhang H., Qiang W., Shekhtman E., Shao D., Revoe D., Villamarin R., Ivanchenko E., Kimura M., et al. ALFA: Allele Frequency Aggregator. National Center for Biotechnology Information. U.S. National Library of Medicine. [(accessed on 8 May 2022)];2020 Available online: www.ncbi.nlm.nih.gov/snp/docs/gsr/alfa.

Mathias R.A., Pani V., Chilton F.H. Genetic Variants in the FADS Gene: Implications for Dietary Recommendations for Fatty Acid Intake. Curr. Nutr. Rep. 2014;3:139–148. doi: 10.1007/s13668-014-0079-1. PubMed DOI PMC

Cormier H., Rudkowska I., Paradis A.M., Thifault E., Garneau V., Lemieux S., Couture P., Vohl M.C. Association between polymorphisms in the fatty acid desaturase gene cluster and the plasma triacylglycerol response to an n-3 PUFA supplementation. Nutrients. 2012;4:1026–1041. doi: 10.3390/nu4081026. PubMed DOI PMC

Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215. doi: 10.1093/nar/16.3.1215. PubMed DOI PMC

Sanger F., Nicklen S., Coulson A.R. DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA. 1977;74:5463–5467. doi: 10.1073/pnas.74.12.5463. PubMed DOI PMC

Kimmel G., Shamir R. Maximum Likelihood Resolution of Multi-block Genotypes; Proceedings of the Eighth Annual International Conference on Research in Computational Molecular Biology—RECOMB 04: San Diego, CA USA; New York, NY, USA. 27–31 March 2004; pp. 2–9. DOI

Kimmel G., Shamir R. GERBIL: Genotype resolution and block identification using likelihood. Proc. Natl. Acad. Sci. USA. 2005;102:158–162. doi: 10.1073/pnas.0404730102. PubMed DOI PMC

Barrett J.C., Fry B., Maller J., Daly M.J. Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–265. doi: 10.1093/bioinformatics/bth457. PubMed DOI

The R Core Team: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria. 2022. [(accessed on 16 April 2022)]. Available online: https://www.R-project.org/

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...