PURPOSE OF REVIEW: Endogenous synthesis of the long-chain polyunsaturated fatty acids (LCPUFAs) is mediated by the fatty acid desaturase (FADS) gene cluster (11q12-13.1) and elongation of very long-chain fatty acids 2 (ELOVL2) (6p24.2) and ELOVL5 (6p12.1). Although older biochemical work identified the product of one gene, FADS2, rate limiting for LCPUFA synthesis, recent studies suggest that polymorphisms in any of these genes can limit accumulation of product LCPUFA. RECENT FINDINGS: Genome-wide association study (GWAS) of Greenland Inuit shows strong adaptation signals within FADS gene cluster, attributed to high omega-3 fatty acid intake, while GWAS found ELOVL2 associated with sleep duration, age and DNA methylation. ELOVL5 coding mutations cause spinocerebellar ataxia 38, and epigenetic marks were associated with depression and suicide risk. Two sterol response element binding sites were found on ELOVL5, a SREBP-1c target gene. Minor allele carriers of a 3 single nucleotide polymorphism (SNP) haplotype in ELOVL2 have decreased 22 : 6n-3 levels. Unequivocal molecular evidence shows mammalian FADS2 catalyzes direct Δ4-desaturation to yield 22 : 6n-3 and 22 : 5n-6. An SNP near FADS1 influences the levels of 5-lipoxygenase products and epigenetic alteration. SUMMARY: Genetic polymorphisms within FADS and ELOVL can limit LCPUFA product accumulation at any step of the biosynthetic pathway.
PURPOSE OF REVIEW: Endogenous synthesis of the long-chain polyunsaturated fatty acids (LCPUFAs) is mediated by the fatty acid desaturase (FADS) gene cluster (11q12-13.1) and elongation of very long-chain fatty acids 2 (ELOVL2) (6p24.2) and ELOVL5 (6p12.1). Although older biochemical work identified the product of one gene, FADS2, rate limiting for LCPUFA synthesis, recent studies suggest that polymorphisms in any of these genes can limit accumulation of product LCPUFA. RECENT FINDINGS: Genome-wide association study (GWAS) of Greenland Inuit shows strong adaptation signals within FADS gene cluster, attributed to high omega-3 fatty acid intake, while GWAS found ELOVL2 associated with sleep duration, age and DNA methylation. ELOVL5 coding mutations cause spinocerebellar ataxia 38, and epigenetic marks were associated with depression and suicide risk. Two sterol response element binding sites were found on ELOVL5, a SREBP-1c target gene. Minor allele carriers of a 3 single nucleotide polymorphism (SNP) haplotype in ELOVL2 have decreased 22 : 6n-3 levels. Unequivocal molecular evidence shows mammalianFADS2 catalyzes direct Δ4-desaturation to yield 22 : 6n-3 and 22 : 5n-6. An SNP near FADS1 influences the levels of 5-lipoxygenase products and epigenetic alteration. SUMMARY: Genetic polymorphisms within FADS and ELOVL can limit LCPUFA product accumulation at any step of the biosynthetic pathway.
Authors: Woo Jung Park; Kumar S D Kothapalli; Holly T Reardon; Peter Lawrence; Shu-Bing Qian; J Thomas Brenna Journal: J Lipid Res Date: 2012-05-22 Impact factor: 5.922
Authors: Luciano Trevizan; Alexandre de Mello Kessler; J Thomas Brenna; Peter Lawrence; Mark K Waldron; John E Bauer Journal: Lipids Date: 2012-01-12 Impact factor: 1.880
Authors: Holly T Reardon; Andrea T Hsieh; Woo Jung Park; Kumar S D Kothapalli; Joshua C Anthony; Peter W Nathanielsz; J Thomas Brenna Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2012-03-06 Impact factor: 4.006
Authors: Holly T Reardon; Jimmy Zhang; Kumar S D Kothapalli; Andrea J Kim; Woo Jung Park; J Thomas Brenna Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2012-06-27 Impact factor: 4.006
Authors: John C Chambers; Weihua Zhang; Joban Sehmi; Xinzhong Li; Mark N Wass; Pim Van der Harst; Hilma Holm; Serena Sanna; Maryam Kavousi; Sebastian E Baumeister; Lachlan J Coin; Guohong Deng; Christian Gieger; Nancy L Heard-Costa; Jouke-Jan Hottenga; Brigitte Kühnel; Vinod Kumar; Vasiliki Lagou; Liming Liang; Jian'an Luan; Pedro Marques Vidal; Irene Mateo Leach; Paul F O'Reilly; John F Peden; Nilufer Rahmioglu; Pasi Soininen; Elizabeth K Speliotes; Xin Yuan; Gudmar Thorleifsson; Behrooz Z Alizadeh; Larry D Atwood; Ingrid B Borecki; Morris J Brown; Pimphen Charoen; Francesco Cucca; Debashish Das; Eco J C de Geus; Anna L Dixon; Angela Döring; Georg Ehret; Gudmundur I Eyjolfsson; Martin Farrall; Nita G Forouhi; Nele Friedrich; Wolfram Goessling; Daniel F Gudbjartsson; Tamara B Harris; Anna-Liisa Hartikainen; Simon Heath; Gideon M Hirschfield; Albert Hofman; Georg Homuth; Elina Hyppönen; Harry L A Janssen; Toby Johnson; Antti J Kangas; Ido P Kema; Jens P Kühn; Sandra Lai; Mark Lathrop; Markus M Lerch; Yun Li; T Jake Liang; Jing-Ping Lin; Ruth J F Loos; Nicholas G Martin; Miriam F Moffatt; Grant W Montgomery; Patricia B Munroe; Kiran Musunuru; Yusuke Nakamura; Christopher J O'Donnell; Isleifur Olafsson; Brenda W Penninx; Anneli Pouta; Bram P Prins; Inga Prokopenko; Ralf Puls; Aimo Ruokonen; Markku J Savolainen; David Schlessinger; Jeoffrey N L Schouten; Udo Seedorf; Srijita Sen-Chowdhry; Katherine A Siminovitch; Johannes H Smit; Timothy D Spector; Wenting Tan; Tanya M Teslovich; Taru Tukiainen; Andre G Uitterlinden; Melanie M Van der Klauw; Ramachandran S Vasan; Chris Wallace; Henri Wallaschofski; H-Erich Wichmann; Gonneke Willemsen; Peter Würtz; Chun Xu; Laura M Yerges-Armstrong; Goncalo R Abecasis; Kourosh R Ahmadi; Dorret I Boomsma; Mark Caulfield; William O Cookson; Cornelia M van Duijn; Philippe Froguel; Koichi Matsuda; Mark I McCarthy; Christa Meisinger; Vincent Mooser; Kirsi H Pietiläinen; Gunter Schumann; Harold Snieder; Michael J E Sternberg; Ronald P Stolk; Howard C Thomas; Unnur Thorsteinsdottir; Manuela Uda; Gérard Waeber; Nicholas J Wareham; Dawn M Waterworth; Hugh Watkins; John B Whitfield; Jacqueline C M Witteman; Bruce H R Wolffenbuttel; Caroline S Fox; Mika Ala-Korpela; Kari Stefansson; Peter Vollenweider; Henry Völzke; Eric E Schadt; James Scott; Marjo-Riitta Järvelin; Paul Elliott; Jaspal S Kooner Journal: Nat Genet Date: 2011-10-16 Impact factor: 38.330
Authors: Damir Zadravec; Petr Tvrdik; Hervé Guillou; Richard Haslam; Tsutomu Kobayashi; Johnathan A Napier; Mario R Capecchi; Anders Jacobsson Journal: J Lipid Res Date: 2010-11-24 Impact factor: 5.922
Authors: H G Park; J Y Zhang; C Foster; D Sudilovsky; D A Schwed; J Mecenas; S Devapatla; P Lawrence; K S D Kothapalli; J T Brenna Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2018-05-16 Impact factor: 4.006
Authors: Jonás I Silva-Marrero; Juliana Villasante; Ania Rashidpour; Mariana Palma; Anna Fàbregas; María Pilar Almajano; Ivan Viegas; John G Jones; Montserrat Miñarro; Josep R Ticó; Isabel V Baanante; Isidoro Metón Journal: Biomolecules Date: 2019-07-24
Authors: Anthony D Gromovsky; Rebecca C Schugar; Amanda L Brown; Robert N Helsley; Amy C Burrows; Daniel Ferguson; Renliang Zhang; Brian E Sansbury; Richard G Lee; Richard E Morton; Daniela S Allende; John S Parks; Matthew Spite; J Mark Brown Journal: Arterioscler Thromb Vasc Biol Date: 2017-10-26 Impact factor: 8.311
Authors: Kumar S D Kothapalli; Hui Gyu Park; Xiaoxian Guo; Xuepeng Sun; James Zou; Stephanie S Hyon; Xia Qin; Peter Lawrence; Rinat R Ran-Ressler; Ji Yao Zhang; Zhenglong Gu; J Thomas Brenna Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2018-06-28 Impact factor: 4.006