Diet-gene interactions and PUFA metabolism: A potential contributor to health disparities and human diseases

Nutrients

Volumn 6, Issue 5, 2014, Pages 1993-2022

  Chilton, Floyd H ^a   Murphy, Robert C ^b   Wilson, Bryan A ^a   Sergeant, Susan ^a   Ainsworth, Hannah ^a   Seeds, Michael C ^a   Mathias, Rasika A ^c  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Arachidonic acid; Cardiovascular disease; Eicosanoids; Fatty acid desaturase (FADS); Genetic variants; Inflammation; Nutrition; Polyunsaturated fatty acids; Single nucleotide polymorphisms

Indexed keywords

ACYL COENZYME A DESATURASE 1; ARACHIDONIC ACID; GAMMA LINOLENIC ACID; ICOSANOID; POLYUNSATURATED FATTY ACID; STEARIDONIC ACID; LINOLEIC ACID; OMEGA 6 FATTY ACID;

BIOSYNTHESIS; CALORIC INTAKE; CARDIOVASCULAR DISEASE; DIET; FATTY ACID METABOLISM; GENE CLUSTER; GENE INTERACTION; GENETIC VARIABILITY; HEALTH DISPARITY; HEART INFARCTION; HUMAN; INFLAMMATION; NONHUMAN; NUTRIGENOMICS; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; AFRICAN AMERICAN; ANIMAL; CARDIOVASCULAR DISEASES; DISEASE MODEL; GENETICS; GENOTYPE ENVIRONMENT INTERACTION; METABOLISM;

AFRICAN AMERICANS; ANIMALS; CARDIOVASCULAR DISEASES; DIET; DISEASE MODELS, ANIMAL; FATTY ACIDS, OMEGA-6; GENE-ENVIRONMENT INTERACTION; HEALTH STATUS DISPARITIES; HUMANS; LINOLEIC ACID; RISK FACTORS;

EID: 84901313698     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu6051993     Document Type: Review

References (151)

1. Cordain, L.; Eaton, S.B.; Sebastian, A.; Mann, N.; Lindeberg, S.; Watkins, B.A.; O'Keefe, J.H.; Brand-Miller, J. Origins and evolution of the Western diet: Health implications for the 21st century. Am. J. Clin. Nutr. 2005, 81, 341-354.
2. Ferrante, A.W., Jr. Obesity-induced inflammation: A metabolic dialogue in the language of inflammation. J. Intern. Med. 2007, 262, 408-414.
3. Hamminga, E.A.; van der Lely, A.J.; Neumann, H.A.; Thio, H.B. Chronic inflammation in psoriasis and obesity: Implications for therapy. Med. Hypotheses 2006, 67, 768-773.
4. Forsythe, L.K.; Wallace, J.M.; Livingstone, M.B. Obesity and inflammation: The effects of weight loss. Nutr. Res. Rev. 2008, 21, 117-133.
5. Nguyen, X.-M.T.; Lane, J.; Smith, B.R.; Nguyen, N.T. Changes in inflammatory biomarkers across weight classes in a representative US population: A link between obesity and inflammation. J. Gastrointest. Surg. 2009, 13, 1205-1212.
6. Calle, E.E.; Thun, M.J. Obesity and cancer. Oncogene 2004, 23, 6365-6378.
7. Beuther, D.A.; Weiss, S.T.; Sutherland, E.R. Obesity and asthma. Am. J. Respir. Crit. Care Med. 2006, 174, 112-119.
8. Naderali, E.K.; Ratcliffe, S.H.; Dale, M.C. Obesity and Alzheimer's disease: A link between body weight and cognitive function in old age. Am. J. Alzheimers Dis. Other. Demen 2009, 24, 445-449.
9. Leveille, S.G.; Wee, C.C.; Iezzoni, L.I. Trends in obesity and arthritis among baby boomers and their predecessors, 1971-2002. Am. J. Public Health 2005, 95, 1607-1613.
10. Sankar, P.; Cho, M.K.; Condit, C.M.; Hunt, L.M.; Koenig, B.; Marshall, P.; Lee, S.S.; Spicer, P. Genetic research and health disparities. JAMA 2004, 291, 2985-2989.
11. Mensah, G.A.; Mokdad, A.H.; Ford, E.S.; Greenlund, K.J.; Croft, J.B. State of disparities in cardiovascular health in the United States. Circulation 2005, 111, 1233-1241.
12. Krieger, N.; Chen, J.T.; Waterman, P.D.; Soobader, M.J.; Subramanian, S.V.; Carson, R. Geocoding and monitoring of US socioeconomic inequalities in mortality and cancer incidence: Does the choice of area-based measure and geographic level matter? The Public Health Disparities Geocoding Project. Am. J. Epidemiol. 2002, 156, 471-482.
13. Braveman, P. Health disparities and health equity: Concepts and measurement. Annu. Rev. Public Health 2006, 27, 167-194.
14. Sankar, P.; Cho, M.K.; Mountain, J. Race and ethnicity in genetic research. Am. J. Med. Genet A 2007, 143A, 961-970.
15. Kuzawa, C.W.; Sweet, E. Epigenetics and the embodiment of race: Developmental origins of US racial disparities in cardiovascular health. Am. J. Hum. Biol. 2009, 21, 2-15.
16. Hibbeln, J.R.; Nieminen, L.R.; Blasbalg, T.L.; Riggs, J.A.; Lands, W.E. Healthy intakes of n-3 and n-6 fatty acids: Estimations considering worldwide diversity. Am. J. Clin. Nutr. 2006, 83, 1483S-1493S.
17. Blasbalg, T.L.; Hibbeln, J.R.; Ramsden, C.E.; Majchrzak, S.F.; Rawlings, R.R. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am. J. Clin. Nutr. 2011, 93, 950-962.
18. Simopoulos, A.P. Importance of the omega-6/omega-3 balance in health and disease: Evolutionary aspects of diet. World Rev. Nutr. Diet 2011, 102, 10-21.
19. Mensink, R.P.; Zock, P.L.; Kester, A.D.; Katan, M.B. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: A meta-analysis of 60 controlled trials. Am. J. Clin. Nutr. 2003, 77, 1146-1155.
20. Siguel, E. A new relationship between total/high density lipoprotein cholesterol and polyunsaturated fatty acids. Lipids 1996, 31, S51-S56.
21. Mensink, R.P.; Katan, M.B. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb. 1992, 12, 911-919.
22. Harris, W.S.; Mozaffarian, D.; Rimm, E.; Kris-Etherton, P.; Rudel, L.L.; Appel, L.J.; Engler, M.M.; Engler, M.B.; Sacks, F. Omega-6 fatty acids and risk for cardiovascular disease: A science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation 2009, 119, 902-907.
23. Ramsden, C.E.; Hibbeln, J.R.; Majchrzak-Hong, S.F. All PUFAs are not created equal: Absence of CHD benefit specific to linoleic acid in randomized controlled trials and prospective observational cohorts. World Rev. Nutr. Diet. 2011, 102, 30-43.
24. Ramsden, C.E.; Hibbeln, J.R.; Majchrzak, S.F.; Davis, J.M. n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: A meta-analysis of randomised controlled trials. Br. J. Nutr. 2010, 104, 1586-1600.
25. Ramsden, C.E.; Zamora, D.; Leelarthaepin, B.; Majchrzak-Hong, S.F.; Faurot, K.R.; Suchindran, C.M.; Ringel, A.; Davis, J.M.; Hibbeln, J.R. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: Evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 2013, 346, e8707.
26. Smith, W.L. The eicosanoids and their biochemical mechanisms of action. Biochem. J. 1989, 259, 315-324.
27. Haeggstrom, J.Z.; Funk, C.D. Lipoxygenase and leukotriene pathways: Biochemistry, biology, and roles in disease. Chem. Rev. 2011, 111, 5866-5898.
28. Wang, D.; Dubois, R.N. Eicosanoids and cancer. Nat. Rev. Cancer 2010, 10, 181-193.
29. Panigrahy, D.; Kalish, B.T.; Huang, S.; Bielenberg, D.R.; Le, H.D.; Yang, J.; Edin, M.L.; Lee, C.R.; Benny, O.; Mudge, D.K.; Butterfield, C.E.; et al. Epoxyeicosanoids promote organ and tissue regeneration. Proc. Natl. Acad. Sci. USA 2013, 110, 13528-13533.
30. Harris, T.R.; Hammock, B.D. Soluble epoxide hydrolase: Gene structure, expression and deletion. Gene 2013, 526, 61-74.
31. Serhan, C.N.; Chiang, N. Resolution phase lipid mediators of inflammation: Agonists of resolution. Curr. Opin. Pharmacol. 2013, 13, 632-640.
32. Innis, S. Maternal nutrition, genetics, and human milk lipids. Curr. Nutr. Rep. 2013, 2, 151-158.
33. Park, W.J.; Kothapalli, K.S.; Lawrence, P.; Tyburczy, C.; Brenna, J.T. An alternate pathway to long-chain polyunsaturates: The FADS2 gene product Delta8-desaturates 20:2n-6 and 20:3n-3. J. Lipid. Res. 2009, 50, 1195-1202.
34. Koletzko, B.; Lattka, E.; Zeilinger, S.; Illig, T.; Steer, C. 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. Am. J. Clin. Nutr. 2011, 93, 211-219.
35. Meyer, B.J.; Mann, N.J.; Lewis, J.L.; Milligan, G.C.; Sinclair, A.J.; Howe, P.R. Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids 2003, 38, 391-398.
36. Calder, P.C. Dietary arachidonic acid: Harmful, harmless or helpful? Br. J. Nutr. 2007, 98, 451-453.
37. Weaver, K.L.; Ivester, P.; Chilton, J.A.; Wilson, M.D.; Pandey, P.; Chilton, F.H. The content of favorable and unfavorable polyunsaturated fatty acids found in commonly eaten fish. J. Am. Diet. Assoc. 2008, 108, 1178-1185.
38. Simopoulos, A.P. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp. Biol. Med. 2008, 233, 674-688.
39. Saravanan, P.; Davidson, N.C.; Schmidt, E.B.; Calder, P.C. Cardiovascular effects of marine omega-3 fatty acids. Lancet 2010, 376, 540-550.
40. Mozaffarian, D.; Wu, J.H. Omega-3 fatty acids and cardiovascular disease: Effects on risk factors, molecular pathways, and clinical events. J. Am. Coll. Cardiol. 2011, 58, 2047-2067.
41. Sprecher, H. Biochemistry of essential fatty acids. Prog. Lipid. Res. 1981, 20, 13-22.
42. Christophersen, B.O.; Hagve, T.A.; Christensen, E.; Johansen, Y.; Tverdal, S. Eicosapentaenoic and arachidonic acid metabolism in isolated liver cells. Scand. J. Clin. Lab. Investing. Suppl. 1986, 184, 55-60.
43. Poisson, J.P.; Dupuy, R.P.; Sarda, P.; Descomps, B.; Narce, M.; Rieu, D.; Crastes de, P.A. Evidence that liver microsomes of human neonates desaturate essential fatty acids. Biochim. Biophys. Acta 1993, 1167, 109-113.
44. Horrobin, D.F. Fatty acid metabolism in health and disease: The role of delta-6-desaturase. Am. J. Clin. Nutr. 1993, 57, 732S-736S.
45. El Boustani, S.; Causse, J.E.; Descomps, B.; Monnier, L.; Mendy, F.; Crastes de, P.A. Direct in vivo characterization of delta 5 desaturase activity in humans by deuterium labeling: Effect of insulin. Metabolism 1989, 38, 315-321.
46. Glaser, C.; Lattka, E.; Rzehak, P.; Steer, C.; Koletzko, B. Genetic variation in polyunsaturated fatty acid metabolism and its potential relevance for human development and health. Matern. Child Nutr. 2011, 7, 27-40.
47. Reardon, H.T.; Zhang, J.; Kothapalli, K.S.; Kim, A.J.; Park, W.J.; Brenna, J.T. Insertion-deletions in a FADS2 intron 1 conserved regulatory locus control expression of fatty acid desaturases 1 and 2 and modulate response to simvastatin. Prostaglandins Leukot. Essent. Fatty Acids 2012, 87, 25-33.
48. Gregory, M.K.; Cleland, L.G.; James, M.J. Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2. J. Lipid. Res. 2013, 54, 2851-2857.
49. Sprecher, H.; Chen, Q. Polyunsaturated fatty acid biosynthesis: A microsomal-peroxisomal process. Prostaglandins Leukot. Essent. Fatty Acids 1999, 60, 317-321.
50. Sprecher, H. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim. Biophys. Acta 2000, 1486, 219-231.
51. Sprecher, H. The roles of anabolic and catabolic reactions in the synthesis and recycling of polyunsaturated fatty acids. Prostaglandins Leukot. Essent. Fatty Acids 2002, 67, 79-83.
52. Hodson, L.; Skeaff, C.M.; Fielding, B.A. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog. Lipid. Res. 2008, 47, 348-380.
53. Gregory, M.K.; Gibson, R.A.; Cook-Johnson, R.J.; Cleland, L.G.; James, M.J. Elongase reactions as control points in long-chain polyunsaturated fatty acid synthesis. PLoS One 2011, 6, e29662.
54. Blank, C.; Neumann, M.A.; Makrides, M.; Gibson, R.A. Optimizing DHA levels in piglets by lowering the linoleic acid to alpha-linolenic acid ratio. J. Lipid Res. 2002, 43, 1537-1543.
55. Gibson, R.A.; Neumann, M.A.; Lien, E.L.; Boyd, K.A.; Tu, W.C. Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids. Prostaglandins Leukot. Essent. Fatty Acids 2013, 88, 139-146.
56. Mohrhauer, H.; Holman, R.T. The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver. J. Lipid Res. 1963, 4, 151-159.
57. Sarkkinen, E.S.; Agren, J.J.; Ahola, I.; Ovaskainen, M.L.; Uusitupa, M.I. Fatty acid composition of serum cholesterol esters, and erythrocyte and platelet membranes as indicators of long-term adherence to fat-modified diets. Am. J. Clin. Nutr. 1994, 59, 364-370.
58. Hussein, N.; Ah-Sing, E.; Wilkinson, P.; Leach, C.; Griffin, B.A.; Millward, D.J. Long-chain conversion of [13C] linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men. J. Lipid Res. 2005, 46, 269-280.
59. Spector, A.A. Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain. J. Mol. Neurosci. 2001, 16, 159-165.
60. Lands, W.E.; Hart, P. Metabolism of glycerolipids. VI. Specificities of acyl coenzyme A: Phospolipid acyltransferases. J. Biol. Chem. 1965, 240, 1905-1911.
61. Chilton, F.H.; Murphy, R.C. Remodeling of arachidonate-containing phosphoglycerides within the human neutrophil. J. Biol. Chem. 1986, 261, 7771-7777.
62. Kang, M.J.; Fujino, T.; Sasano, H.; Minekura, H.; Yabuki, N.; Nagura, H.; Iijima, H.; Yamamoto, T.T. A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of the rat adrenal, ovary, and testis. Proc. Natl. Acad. Sci. USA 1997, 94, 2880-2884.
63. Matsuda, S.; Inoue, T.; Lee, H.C.; Kono, N.; Tanaka, F.; Gengyo-Ando, K.; Mitani, S.; Arai, H. Member of the membrane-bound O-acyltransferase (MBOAT) family encodes a lysophospholipid acyltransferase with broad substrate specificity. Genes Cells 2008, 13, 879-888.
64. Chilton, F.H.; Fonteh, A.N.; Surette, M.E.; Triggiani, M.; Winkler, J.D. Control of arachidonate levels within inflammatory cells. Biochim. Biophys. Acta 1996, 1299, 1-15.
65. Astudillo, A.M.; Balgoma, D.; Balboa, M.A.; Balsinde, J. Dynamics of arachidonic acid mobilization by inflammatory cells. Biochim. Biophys. Acta 2012, 1821, 249-256.
66. 2+-dependent translocation domain with homology to PKC and GAP. Cell 1991, 65, 1043-1051.
67. 2 enzymes: An update. Biochimie 2013, 95, 43-50.
68. Oskolkova, O.V.; Afonyushkin, T.; Preinerstorfer, B.; Bicker, W.; von, S.E.; Hainzl, E.; Demyanets, S.; Schabbauer, G.; Lindner, W.; Tselepis, A.D.; et al. Oxidized phospholipids are more potent antagonists of lipopolysaccharide than inducers of inflammation. J. Immunol. 2010, 185, 7706-7712.
69. Schmitz, G.; Ecker, J. The opposing effects of n-3 and n-6 fatty acids. Prog. Lipid. Res. 2008, 47, 147-155.
70. Boyce, J.A. Eicosanoids in asthma, allergic inflammation, and host defense. Curr. Mol. Med. 2008, 8, 335-349.
71. Calder, P.C. Long chain fatty acids and gene expression in inflammation and immunity. Curr. Opin. Clin. Nutr. Metab. Care 2013, 16, 425-433.
72. Soberman, R.J.; Christmas, P. The organization and consequences of eicosanoid signaling. J. Clin. Investig. 2003, 111, 1107-1113.
73. Chinetti, G.; Fruchart, J.C.; Staels, B. Peroxisome proliferator-activated receptors (PPARs): Nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm. Res. 2000, 49, 497-505.
74. Jump, D.B.; Clarke, S.D. Regulation of gene expression by dietary fat. Annu. Rev. Nutr. 1999, 19, 63-90.
75. Deckelbaum, R.J.; Worgall, T.S.; Seo, T. n-3 Fatty acids and gene expression. Am. J. Clin. Nutr. 2006, 83, 1520S-1525S.
76. Jung, U.J.; Torrejon, C.; Chang, C.L.; Hamai, H.; Worgall, T.S.; Deckelbaum, R.J. Fatty acids regulate endothelial lipase and inflammatory markers in macrophages and in mouse aorta: A role for PPARgamma. Arterioscler. Thromb. Vasc. Biol. 2012, 32, 2929-2937.
77. Berger, A.; Roberts, M.A.; Hoff, B. How dietary arachidonic-and docosahexaenoic-acid rich oils differentially affect the murine hepatic transcriptome. Lipids Health Dis. 2006, 5, 10.
78. Caputo, M.; Zirpoli, H.; Torino, G.; Tecce, M.F. Selective regulation of UGT1A1 and SREBP-1c mRNA expression by docosahexaenoic, eicosapentaenoic, and arachidonic acids. J. Cell Physiol. 2011, 226, 187-193.
79. Vanden Heuvel, J.P. Nutrigenomics and nutrigenetics of omega-3 polyunsaturated fatty acids. Prog. Mol. Biol. Transl. Sci. 2012, 108, 75-112.
80. Alvheim, A.R.; Malde, M.K.; Osei-Hyiaman, D.; Lin, Y.H.; Pawlosky, R.J.; Madsen, L.; Kristiansen, K.; Froyland, L.; Hibbeln, J.R. Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity. Obesity 2012, 20, 1984-1994.
81. Innis, S.M. Dietary omega 3 fatty acids and the developing brain. Brain Res. 2008, 1237, 35-43.
82. Bradbury, J. Docosahexaenoic acid (DHA): An ancient nutrient for the modern human brain. Nutrients 2011, 3, 529-554.
83. Salem, N., Jr.; Litman, B.; Kim, H.Y.; Gawrisch, K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 2001, 36, 945-959.
84. Komatsu, W.; Ishihara, K.; Murata, M.; Saito, H.; Shinohara, K. Docosahexaenoic acid suppresses nitric oxide production and inducible nitric oxide synthase expression in interferon-gamma plus lipopolysaccharide-stimulated murine macrophages by inhibiting the oxidative stress. Free Radic. Biol. Med. 2003, 34, 1006-1016.
85. Spencer, L.; Mann, C.; Metcalfe, M.; Webb, M.; Pollard, C.; Spencer, D.; Berry, D.; Steward, W.; Dennison, A. The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur. J. Cancer 2009, 45, 2077-2086.
86. Serhan, C.N.; Hong, S.; Gronert, K.; Colgan, S.P.; Devchand, P.R.; Mirick, G.; Moussignac, R.L. Resolvins: A family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 2002, 196, 1025-1037.
87. Serhan, C.N.; Arita, M.; Hong, S.; Gotlinger, K. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids 2004, 39, 1125-1132.
88. Ariel, A.; Serhan, C.N. Resolvins and protectins in the termination program of acute inflammation. Trends Immunol. 2007, 28, 176-183.
89. Spector, A.A. Essentiality of fatty acids. Lipids 1999, 34, S1-S3.
90. Calder, P.C. The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability. Mol. Nutr. Food Res. 2012, 56, 1073-1080.
91. Smith, W.L. Cyclooxygenases, peroxide tone and the allure of fish oil. Curr. Opin. Cell Biol. 2005, 17, 174-182.
92. Smith, W.L. Nutritionally essential fatty acids and biologically indispensable cyclooxygenases. Trends Biochem. Sci. 2008, 33, 27-37.
93. Terano, T.; Salmon, J.A.; Moncada, S. Biosynthesis and biological activity of leukotriene B5. Prostaglandins 1984, 27, 217-232.
94. Balvers, M.G.; Verhoeckx, K.C.; Bijlsma, S.; Rubingh, C.M.; Meijerink, J.; Wortelboer, H.M.; Witkamp, R.F. Fish oil and inflammatory status alter the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes in mouse plasma and tissues. Metabolomics 2012, 8, 1130-1147.
95. Marquardt, A.; Stohr, H.; White, K.; Weber, B.H.F. CDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics 2000, 66, 175-183.
96. Nakamura, M.T.; Nara, T.Y. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu. Rev. Nutr. 2004, 24, 345-376.
97. Schadt, E.E. Molecular networks as sensors and drivers of common human diseases. Nature 2009, 461, 218-223.
98. Gieger, C.; Geistlinger, L.; Altmaier, E.; Hrabe de, A.M.; Kronenberg, F.; Meitinger, T.; Mewes, H.W.; Wichmann, H.E.; Weinberger, K.M.; Adamski, J.; et al. Genetics meets metabolomics: A genome-wide association study of metabolite profiles in human serum. PLoS Genet 2008, 4, e1000282.
99. Illig, T.; Gieger, C.; Zhai, G.; Romisch-Margl, W.; Wang-Sattler, R.; Prehn, C.; Altmaier, E.; Kastenmuller, G.; Kato, B.S.; Mewes, H.W.; et al. A genome-wide perspective of genetic variation in human metabolism. Nat. Genet 2010, 42, 137-141.
100. Kathiresan, S.; Melander, O.; Guiducci, C.; Surti, A.; Burtt, N.P.; Rieder, M.J.; Cooper, G.M.; Roos, C.; Voight, B.F.; Havulinna, A.S.; et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat. Genet 2008, 40, 189-197.
101. Willer, C.J.; Sanna, S.; Jackson, A.U.; Scuteri, A.; Bonnycastle, L.L.; Clarke, R.; Heath, S.C.; Timpson, N.J.; Najjar, S.S.; Stringham, H.M.; et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat. Genet 2008, 40, 161-169.
102. 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.
103. Aulchenko, Y.S.; Ripatti, S.; Lindqvist, I.; Boomsma, D.; Heid, I.M.; Pramstaller, P.P.; Penninx, B.W.; Janssens, A.C.; Wilson, J.F.; Spector, T.; et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat. Genet 2009, 41, 47-55.
104. Teslovich, T.M.; Musunuru, K.; Smith, A.V.; Edmondson, A.C.; Stylianou, I.M.; Koseki, M.; Pirruccello, J.P.; Ripatti, S.; Chasman, D.I.; Willer, C.J.; et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010, 466, 707-713.
105. 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.
106. Xie, L.; Innis, S.M. 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. J. Nutr. 2008, 138, 2222-2228.
107. Schaeffer, L.; Gohlke, H.; Muller, 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.
108. Rzehak, P.; Heinrich, J.; Klopp, N.; Schaeffer, L.; Hoff, S.; Wolfram, G.; Illig, T.; Linseisen, J. Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 (FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes. Br. J. Nutr. 2009, 101, 20-26.
109. Bokor, S.; Dumont, J.; Spinneker, A.; Gonzalez-Gross, M.; Nova, E.; Widhalm, K.; Moschonis, G.; Stehle, P.; Amouyel, P.; De, H.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.
110. De Antueno, R.J.; Knickle, L.C.; Smith, H.; Elliot, M.L.; Allen, S.J.; Nwaka, S.; Winther, M.D. Activity of human Delta5 and Delta6 desaturases on multiple n-3 and n-6 polyunsaturated fatty acids. FEBS Lett. 2001, 509, 77-80.
111. Mathias, R.A.; Vergara, C.; Gao, L.; Rafaels, N.; Hand, T.; Campbell, M.; Bickel, C.; Ivester, P.; Sergeant, S.; Barnes, K.C.; et al. FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. J. Lipid Res. 2010, 51, 2766-2774.
112. Mathias, R.A.; Sergeant, S.; Ruczinski, I.; Torgerson, D.G.; Hugenschmidt, C.E.; Kubala, M.; Vaidya, D.; Suktitipat, B.; Ziegler, J.T.; Ivester, P.; et al. The impact of FADS genetic variants on omega6 polyunsaturated fatty acid metabolism in African Americans. BMC Genet 2011, 12, 50.
113. 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 or the metabolic syndrome. Br. J. Nutr. 2012, 107, 547-555.
114. Tanaka, T.; Shen, J.; Abecasis, G.R.; Kisialiou, A.; Ordovas, J.M.; Guralnik, J.M.; Singleton, A.; Bandinelli, S.; Cherubini, A.; Arnett, D.; et al. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet 2009, 5, e1000338.
115. Lemaitre, R.N.; Tanaka, T.; Tang, W.; Manichaikul, A.; Foy, M.; Kabagambe, E.K.; Nettleton, J.A.; King, I.B.; Weng, L.C.; Bhattacharya, S.; et al. Genetic loci associated with plasma phospholipid n-3 fatty acids: A meta-analysis of genome-wide association studies from the CHARGE Consortium. PLoS Genet 2011, 7, e1002193.
116. Lattka, E.; Illig, T.; Heinrich, J.; Koletzko, B. Do FADS genotypes enhance our knowledge about fatty acid related phenotypes? Clin. Nutr. 2010, 29, 277-287.
117. Baylin, A.; Ruiz-Narvaez, E.; Kraft, P.; Campos, H. Alpha-Linolenic acid, Delta6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction. Am. J. Clin. Nutr. 2007, 85, 554-560.
118. 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 omega6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease. Atherosclerosis 2011, 214, 94-100.
119. 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.
120. Li, S.W.; Lin, K.; Ma, P.; Zhang, Z.L.; Zhou, Y.D.; Lu, S.Y.; Zhou, X.; Liu, S.M. FADS gene polymorphisms confer the risk of coronary artery disease in a Chinese Han population through the altered desaturase activities: Based on high-resolution melting analysis. PLoS One 2013, 8, e55869.
121. Lu, Y.; Vaarhorst, A.; Merry, A.H.; Dolle, M.E.; Hovenier, R.; Imholz, S.; Schouten, L.J.; Heijmans, B.T.; Muller, M.; Slagboom, P.E.; et al. Markers of endogenous desaturase activity and risk of coronary heart disease in the CAREMA cohort study. PLoS One 2012, 7, e41681.
122. Schwedhelm, E.; Bartling, A.; Lenzen, H.; Tsikas, D.; Maas, R.; Brummer, J.; Gutzki, F.M.; Berger, J.; Frolich, J.C.; Boger, R.H. Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: A matched case-control study. Circulation 2004, 109, 843-848.
123. Wolfram, R.; Oguogho, A.; Palumbo, B.; Sinzinger, H. Enhanced oxidative stress in coronary heart disease and chronic heart failure as indicated by an increased 8-epi-PGF(2 alpha). Eur. J. Heart Fail 2005, 7, 167-172.
124. Park, J.Y.; Paik, J.K.; Kim, O.Y.; Chae, J.S.; Jang, Y.; Lee, J.H. Interactions between the APOA5-1131 T > C and the FEN1 10154 G > T polymorphisms on omega6 polyunsaturated fatty acids in serum phospholipids and coronary artery disease. J. Lipid. Res. 2010, 51, 3281-3288.
125. 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.
126. Reardon, H.T.; Hsieh, A.T.; Park, W.J.; Kothapalli, K.S.; Anthony, J.C.; Nathanielsz, P.W.; Brenna, J.T. Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts. Prostaglandins Leukot. Essent. Fatty Acids 2013, 88, 15-19.
127. Lattka, E.; Eggers, S.; Moeller, G.; Heim, K.; Weber, M.; Mehta, D.; Prokisch, H.; Illig, T.; Adamski, J. A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1. J. Lipid Res. 2010, 51, 182-191.
128. Von, S.C.; Fischer, S.; Weber, P.C. Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans. J. Clin. Investig. 1985, 76, 1626-1631.
129. Wijendran, V.; Downs, I.; Srigley, C.T.; Kothapalli, K.S.; Park, W.J.; Blank, B.S.; Zimmer, J.P.; Butt, C.M.; Salem, N., Jr.; Brenna, J.T. Dietary arachidonic acid and docosahexaenoic acid regulate liver fatty acid desaturase (FADS) alternative transcript expression in suckling piglets. Prostaglandins Leukot. Essent. Fatty Acids 2013, 89, 345-350.
130. Garagnani, P.; Bacalini, M.G.; Pirazzini, C.; Gori, D.; Giuliani, C.; Mari, D.; Di Blasio, A.M.; Gentilini, D.; Vitale, G.; Collino, S.; et al. Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell 2012, 11, 1132-1134.
131. Helgadottir, A.; Gretarsdottir, S.; St, C.D.; Manolescu, A.; Cheung, J.; Thorleifsson, G.; Pasdar, A.; Grant, S.F.; Whalley, L.J.; Hakonarson, H.; Thorsteinsdottir, U.; et al. Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population. Am. J. Hum. Genet 2005, 76, 505-509.
132. Helgadottir, A.; Manolescu, A.; Thorleifsson, G.; Gretarsdottir, S.; Jonsdottir, H.; Thorsteinsdottir, U.; Samani, N.J.; Gudmundsson, G.; Grant, S.F.; Thorgeirsson, G.; et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat. Genet 2004, 36, 233-239.
133. Lohmussaar, E.; Gschwendtner, A.; Mueller, J.C.; Org, T.; Wichmann, E.; Hamann, G.; Meitinger, T.; Dichgans, M. ALOX5AP gene and the PDE4D gene in a central European population of stroke patients. Stroke 2005, 36, 731-736.
134. Funk, C.D. Leukotriene modifiers as potential therapeutics for cardiovascular disease. Nat. Rev. Drug Discov. 2005, 4, 664-672.
135. Riccioni, G.; Back, M.; Capra, V. Leukotrienes and atherosclerosis. Curr. Drug Targets 2010, 11, 882-887.
136. Mehrabian, M.; Allayee, H.; Wong, J.; Shi, W.; Wang, X.P.; Shaposhnik, Z.; Funk, C.D.; Lusis, A.J. Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ. Res. 2002, 91, 120-126.
137. Drazen, J.M.; Yandava, C.N.; Dube, L.; Szczerback, N.; Hippensteel, R.; Pillari, A.; Israel, E.; Schork, N.; Silverman, E.S.; Katz, D.A.; et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat. Genet 1999, 22, 168-170.
138. Dwyer, J.H.; Allayee, H.; Dwyer, K.M.; Fan, J.; Wu, H.; Mar, R.; Lusis, A.J.; Mehrabian, M. Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N. Engl. J. Med. 2004, 350, 29-37.
139. Allayee, H.; Baylin, A.; Hartiala, J.; Wijesuriya, H.; Mehrabian, M.; Lusis, A.J.; Campos, H. Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction. Am. J. Clin. Nutr. 2008, 88, 934-940.
140. Hartiala, J.; Li, D.; Conti, D.V.; Vikman, S.; Patel, Y.; Tang, W.H.; Brennan, M.L.; Newman, J.W.; Stephensen, C.B.; Armstrong, P.; et al. Genetic contribution of the leukotriene pathway to coronary artery disease. Hum. Genet 2011, 129, 617-627.
141. Hartiala, J.; Gilliam, E.; Vikman, S.; Campos, H.; Allayee, H. Association of PLA2G4A with myocardial infarction is modulated by dietary PUFAs. Am. J. Clin. Nutr. 2012, 95, 959-965.
142. Johnson, G.H.; Fritsche, K. Effect of dietary linoleic acid on markers of inflammation in healthy persons: A systematic review of randomized controlled trials. J. Acad. Nutr. Diet 2012, 112, 1029-1041.
143. Ferrucci, L.; Cherubini, A.; Bandinelli, S.; Bartali, B.; Corsi, A.; Lauretani, F.; Martin, A.; Andres-Lacueva, C.; Senin, U.; Guralnik, J.M. Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J. Clin. Endocrinol. Metab. 2006, 91, 439-446.
144. Montoya, M.T.; Porres, A.; Serrano, S.; Fruchart, J.C.; Mata, P.; Gerique, J.A.; Castro, G.R. Fatty acid saturation of the diet and plasma lipid concentrations, lipoprotein particle concentrations, and cholesterol efflux capacity. Am. J. Clin. Nutr. 2002, 75, 484-491.
145. Chan, J.K.; McDonald, B.E.; Gerrard, J.M.; Bruce, V.M.; Weaver, B.J.; Holub, B.J. Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis. Lipids 1993, 28, 811-817.
146. Thijssen, M.A.; Mensink, R.P. Small differences in the effects of stearic acid, oleic acid, and linoleic acid on the serum lipoprotein profile of humans. Am. J. Clin. Nutr. 2005, 82, 510-516.
147. Liou, Y.A.; King, D.J.; Zibrik, D.; Innis, S.M. Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men. J. Nutr. 2007, 137, 945-952.
148. Lands, W.E.; Morris, A.; Libelt, B. Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues. Lipids 1990, 25, 505-516.
149. Mathias, R.A.; Fu, W.Q.; Akey, J.M.; Ainsworth, H.C.; Torgerson, D.G.; Ruczinski, I.; Sergeant, S.; Barnes, K.C.; Chilton, F.H. Adaptive Evolution of the FADS Gene Cluster within Africa. PLoS One 2012, 7, e44926.
150. Armstrong, P.; Kelley, D.S.; Newman, J.W.; Staggers, F.E., Sr.; Hartiala, J.; Allayee, H.; Stephensen, C.B. Arachidonate 5-lipoxygenase gene variants affect response to fish oil supplementation by healthy African Americans. J. Nutr. 2012, 142, 1417-1428.
151. 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.