{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FADS1 encodes Δ5‐desaturase, a key enzyme that regulates the endogenous synthesis of long‐chain polyunsaturated fatty acids (LC‐PUFAs). In particular, FADS1 catalyzes the conversion of dihomo‐γ–linolenic acid (DGLA) to arachidonic acid (AA), thereby exerting a central role in determining the balance of precursor and product fatty acids that subsequently influence inflammatory eicosanoid synthesis and lipid signaling. Multiple genome‐wide association studies have implicated FADS1 variants in modulating glycemic traits, insulin secretion, and circulating lipid profiles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In parallel, research focusing on fatty acid metabolism has demonstrated that polymorphisms in the FADS1–FADS2 cluster strongly influence the levels of AA and other LC‐PUFAs in blood and cell membranes, underscoring their importance in inflammatory and metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Additionally, associations between FADS1 variants and altered fatty acid profiles extend to impacts on early insulin secretion, inflammatory responses, and even predisposition to diseases such as type 2 diabetes and nonalcoholic fatty liver disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": " Population‐based studies further reveal that differences in allele frequencies—such as those observed between individuals of African and European descent—contribute to variations in AA levels and desaturase efficiency, suggesting that FADS1 genetic diversity may underpin differences in LC‐PUFA status and related disease risks across ethnic groups."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Finally, comprehensive reviews integrating these genetic and metabolic findings confirm that FADS1 is a pivotal determinant of PUFA conversion efficiency, linking dietary fatty acid intake with cellular lipid composition and function, and thereby influencing diverse physiological processes including inflammation, insulin sensitivity, and cell signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Josée Dupuis, Claudia Langenberg, Inga Prokopenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.520"}], "href": "https://doi.org/10.1038/ng.520"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20081858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20081858"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thomas Illig, Christian Gieger, Guangju Zhai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide perspective of genetic variation in human metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.507"}], "href": "https://doi.org/10.1038/ng.507"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20037589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20037589"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Erik Ingelsson, Claudia Langenberg, Marie-France Hivert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db09-1568"}], "href": "https://doi.org/10.2337/db09-1568"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20185807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20185807"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Linda Schaeffer, Henning Gohlke, Martina Müller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl117"}], "href": "https://doi.org/10.1093/hmg/ddl117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16670158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16670158"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nicola Martinelli, Domenico Girelli, Giovanni Malerba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Nutr (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ajcn/88.4.941"}], "href": "https://doi.org/10.1093/ajcn/88.4.941"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18842780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18842780"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Giovanni Malerba, Linda Schaeffer, Luciano Xumerle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lipids (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11745-008-3158-5"}], "href": "https://doi.org/10.1007/s11745-008-3158-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18320251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18320251"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Szilvia Bokor, Julie Dumont, Andre Spinneker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M006205"}], "href": "https://doi.org/10.1194/jlr.M006205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20427696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20427696"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lin Xie, Sheila M Innis "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3945/jn.108.096156"}], "href": "https://doi.org/10.3945/jn.108.096156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18936223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18936223"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Eva Lattka, Thomas Illig, Berthold Koletzko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Opin Lipidol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MOL.0b013e3283327ca8"}], "href": "https://doi.org/10.1097/MOL.0b013e3283327ca8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19809313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19809313"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Berthold Koletzko, Eva Lattka, Sonja Zeilinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon Longitudinal Study of Parents and Children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Nutr (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3945/ajcn.110.006189"}], "href": "https://doi.org/10.3945/ajcn.110.006189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21106917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21106917"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Federica Tosi, Filippo Sartori, Patrizia Guarini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delta-5 and delta-6 desaturases: crucial enzymes in polyunsaturated fatty acid-related pathways with pleiotropic influences in health and disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-3-319-07320-0_7"}], "href": "https://doi.org/10.1007/978-3-319-07320-0_7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25038994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25038994"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Rasika A Mathias, Susan Sergeant, Ingo Ruczinski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2156-12-50"}], "href": "https://doi.org/10.1186/1471-2156-12-50"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21599946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21599946"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Diana M Merino, Holly Johnston, Shannon Clarke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2011.02.012"}], "href": "https://doi.org/10.1016/j.ymgme.2011.02.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21414826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21414826"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Susan Sergeant, Christina E Hugenschmidt, Megan E Rudock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Nutr (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0007114511003230"}], "href": "https://doi.org/10.1017/S0007114511003230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21733300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21733300"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Claudia Glaser, Eva Lattka, Peter Rzehak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in polyunsaturated fatty acid metabolism and its potential relevance for human development and health."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Matern Child Nutr (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1740-8709.2011.00319.x"}], "href": "https://doi.org/10.1111/j.1740-8709.2011.00319.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21366865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21366865"}]}]}]}