1932

Abstract

Variants in the gene cluster modify the activity of polyunsaturated fatty acid (PUFA) desaturation and the lipid composition in human blood and tissue. variants have been associated with plasma lipid concentrations, risk of cardiovascular diseases, overweight, eczema, pregnancy outcomes, and cognitive function. Studies on variations in the genecluster provided some of the first examples for marked gene–diet interactions in modulating complex phenotypes, such as eczema, asthma, and cognition. Genotype distribution differs markedly among ethnicities, apparently reflecting an evolutionary advantage of genotypes enabling active long-chain PUFA synthesis when the introduction of agriculture provided diets rich in linoleic acid but with little arachidonic and eicosapentaenoic acids. Discovering differential effects of PUFA supply that depend on variation of genotypes could open new opportunities for developing precision nutrition strategies based either on an individual's genotype or on genotype distributions in specific populations.

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2019-08-21
2024-10-11
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Literature Cited

  1. 1.
    Ameur A, Enroth S, Johansson A, Zaboli G, Igl W et al. 2012. 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. 90:809–20
    [Google Scholar]
  2. 2.
    Amorim CE, Nunes K, Meyer D, Comas D, Bortolini MC et al. 2017. Genetic signature of natural selection in first Americans. PNAS 114:2195–99
    [Google Scholar]
  3. 3.
    Andersen KR, Harslof LB, Schnurr TM, Hansen T, Hellgren LI et al. 2017. A study of associations between early DHA status and fatty acid desaturase (FADS) SNP and developmental outcomes in children of obese mothers. Br. J. Nutr. 117:278–86
    [Google Scholar]
  4. 4.
    Barman M, Jonsson K, Sandin A, Wold AE, Sandberg AS 2014. Serum fatty acid profile does not reflect seafood intake in adolescents with atopic eczema. Acta Paediatr 103:968–76
    [Google Scholar]
  5. 5.
    Bernard JY, Pan H, Aris IM, Moreno-Betancur M, Soh SE et al. 2018. Long-chain polyunsaturated fatty acids, gestation duration, and birth size: a Mendelian randomization study using fatty acid desaturase variants. Am. J. Clin. Nutr. 108:92–100
    [Google Scholar]
  6. 6.
    Brayner B, Kaur G, Keske MA, Livingstone KM 2018. FADS polymorphism, omega-3 fatty acids and diabetes risk: a systematic review. Nutrients 10:758
    [Google Scholar]
  7. 7.
    Buckley MT, Racimo F, Allentoft ME, Jensen MK, Jonsson A et al. 2017. Selection in Europeans on fatty acid desaturases associated with dietary changes. Mol. Biol. Evol. 34:1307–18
    [Google Scholar]
  8. 8.
    Burdge GC, Wootton SA. 2002. Conversion of α-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br. J. Nutr. 88:411–20
    [Google Scholar]
  9. 9.
    Cadenhead KS, Minichino A, Kelsven S, Addington J, Bearden C et al. 2019. Metabolic abnormalities and low dietary omega 3 are associated with symptom severity and worse functioning prior to the onset of psychosis: findings from the North American Prodrome Longitudinal Studies Consortium. Schizophr. Res. 204:96–103
    [Google Scholar]
  10. 10.
    Caspi A, Williams B, Kim-Cohen J, Craig IW, Milne BJ et al. 2007. Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. PNAS 104:18860–65
    [Google Scholar]
  11. 11.
    Chilton FH, Dutta R, Reynolds LM, Sergeant S, Mathias RA, Seeds MC 2017. Precision nutrition and omega-3 polyunsaturated fatty acids: a case for personalized supplementation approaches for the prevention and management of human diseases. Nutrients 9:1165
    [Google Scholar]
  12. 12.
    Collins CT, Makrides M, McPhee AJ, Sullivan TR, Davis PG et al. 2017. Docosahexaenoic acid and bronchopulmonary dysplasia in preterm infants. N. Engl. J. Med. 376:1245–55
    [Google Scholar]
  13. 13.
    Colombo J, Carlson SE, Cheatham CL, Shaddy DJ, Kerling EH et al. 2013. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Am. J. Clin. Nutr. 98:403–12
    [Google Scholar]
  14. 14.
    Cribb L, Murphy J, Froud A, Oliver G, Bousman CA et al. 2018. Erythrocyte polyunsaturated fatty acid composition is associated with depression and FADS genotype in Caucasians. Nutr. Neurosci. 21:589–601
    [Google Scholar]
  15. 15.
    de la Garza Puentes A, Montes Goyanes R, Chisaguano Tonato AM, Torres-Espínola FJ, Arias García M et al. 2017. Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels—the PREOBE follow-up. PLOS ONE 12:e0179135
    [Google Scholar]
  16. 16.
    Demmelmair H, Koletzko B. 2015. Importance of fatty acids in the perinatal period. World Rev. Nutr. Diet. 112:31–47
    [Google Scholar]
  17. 17.
    Dessi M, Noce A, Bertucci P, Manca di Villahermosa S, Zenobi R et al. 2013. Atherosclerosis, dyslipidemia, and inflammation: the significant role of polyunsaturated fatty acids. ISRN Inflamm 2013:191823
    [Google Scholar]
  18. 18.
    Ding Z, Liu GL, Li X, Chen XY, Wu YX et al. 2016. Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers. Prostaglandins Leukot. Essent. Fatty Acids 109:66–71
    [Google Scholar]
  19. 19.
    Duchen K, Bjorksten B. 2001. Polyunsaturated n-3 fatty acids and the development of atopic disease. Lipids 36:1033–42
    [Google Scholar]
  20. 20.
    Elagizi A, Lavie CJ, Marshall K, DiNicolantonio JJ, O'Keefe JH, Milani RV 2018. Omega-3 polyunsaturated fatty acids and cardiovascular health: a comprehensive review. Prog. Cardiovasc. Dis. 61:76–85
    [Google Scholar]
  21. 21.
    Eur. Comm 2016. Commission Delegated Regulation (EU) 2016/127 of 25 September 2015 supplementing Regulation (EU) No 609/2013 of the European Parliament and of the Council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. Off. J. Eur. Union 2016.L25–1
    [Google Scholar]
  22. 22.
    Eur. Food Saf. Auth 2010. Scientific Opinion on dietary reference values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA J 8:1461
    [Google Scholar]
  23. 23.
    FAO (Food Agric. Organ. U. N.) 2010. Fats and Fatty Acids in Human Nutrition: Report of an Expert Consultation Rome: FAO
    [Google Scholar]
  24. 24.
    Fidler N, Sauerwald T, Pohl A, Demmelmair H, Koletzko B 2000. Docosahexaenoic acid transfer into human milk after dietary supplementation: a randomized clinical trial. J. Lipid Res. 41:1376–83
    [Google Scholar]
  25. 25.
    Glaser C, Heinrich J, Koletzko B 2010. Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism. Metabolism 59:993–99
    [Google Scholar]
  26. 26.
    Goldring MB, Berenbaum F. 2004. The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clin. Orthop. Relat. Res. 427:Suppl.S37–46
    [Google Scholar]
  27. 27.
    Gonzalez-Casanova I, Rzehak P, Stein AD, Garcia Feregrino R, Rivera Dommarco JA et al. 2016. Maternal single nucleotide polymorphisms in the fatty acid desaturase 1 and 2 coding regions modify the impact of prenatal supplementation with DHA on birth weight. Am. J. Clin. Nutr. 103:1171–78
    [Google Scholar]
  28. 28.
    Gonzalez-Casanova I, Schoen M, Rzehak P, Stein AD, Barraza-Villarreal A et al. 2019. Maternal fatty acid desaturase single nucleotide polymorphism modifies the impact of prenatal docosahexaenoic acid supplementation on offspring cognitive development at 5 years. Curr. Dev. Nutr. In press
    [Google Scholar]
  29. 29.
    Grote V, Verduci E, Scaglioni S, Vecchi F, Contarini G et al. 2016. Breast milk composition and infant nutrient intakes during the first 12 months of life. Eur. J. Clin. Nutr. 70:250–56
    [Google Scholar]
  30. 30.
    Heinrich J. 2017. Modulation of allergy risk by breast feeding. Curr. Opin. Clin. Nutr. Metab. Care 20:217–21
    [Google Scholar]
  31. 31.
    Horta BL, Victora CG. 2013. Long-Term Effects of Breastfeeding: A Systematic Review Geneva: World Health Organ.
    [Google Scholar]
  32. 32.
    Hovsepian S, Javanmard SH, Mansourian M, Tajadini M, Hashemipour M, Kelishadi R 2018. Relationship of lipid regulatory gene polymorphisms and dyslipidemia in a pediatric population: the CASPIAN III study. Hormones 17:97–105
    [Google Scholar]
  33. 33.
    Hsieh AT, Brenna JT. 2009. Dietary docosahexaenoic acid but not arachidonic acid influences central nervous system fatty acid status in baboon neonates. Prostaglandins Leukot. Essent. Fatty Acids 81:105–10
    [Google Scholar]
  34. 34.
    Jasani B, Simmer K, Patole SK, Rao SC 2017. Long chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst. Rev. 3:CD000376
    [Google Scholar]
  35. 35.
    Kar S, Wong M, Rogozinska E, Thangaratinam S 2016. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies. Eur. J. Obstet. Gynecol. Reprod. Biol. 198:40–46
    [Google Scholar]
  36. 36.
    Koletzko B. 2016. Human milk lipids. Ann. Nutr. Metab. 69:28–40
    [Google Scholar]
  37. 37.
    Koletzko B, Boey CCM, Campoy C, Carlson SE, Chang N et al. 2014. Current information and Asian perspectives on long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: systematic review and practice recommendations from an Early Nutrition Academy workshop. Ann. Nutr. Metab. 65:49–80
    [Google Scholar]
  38. 38.
    Koletzko B, Bremer HJ. 1989. Fat content and fatty acid composition of infant formulas. Acta Paediatr. Scand. 78:513–21
    [Google Scholar]
  39. 39.
    Koletzko B, Carlson SE, van Goudoever JB 2015. Should infant formula provide both omega-3 DHA and omega-6 arachidonic acid?. Ann. Nutr. Metab. 66:137–38
    [Google Scholar]
  40. 40.
    Koletzko B, Lattka E, Zeilinger S, Illig T, Steer C 2011. 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. 93:211–19
    [Google Scholar]
  41. 41.
    Koletzko B, Lien E, Agostoni C, Bohles H, Campoy C et al. 2008. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J. Perinat. Med. 36:5–14
    [Google Scholar]
  42. 42.
    Koletzko B, Poindexter B, Uauy R 2014. Recommended nutrient intake levels for stable, fully enterally fed very low birthweight infants. Nutritional Care of Preterm Infants: Scientific Basis and Practical Guidelines B Koletzko, B Poindexter, R Uauy 300–5 Basel, Switz: Karger
    [Google Scholar]
  43. 43.
    Koletzko B, Rodriguez-Palmero M, Demmelmair H, Fidler N, Jensen R, Sauerwald T 2001. Physiological aspects of human milk lipids. Early Hum. Dev. 65:Suppl.S3–18
    [Google Scholar]
  44. 44.
    Kramer MS, Matush L, Vanilovich I, Platt R, Bogdanovich N et al. 2007. Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial. BMJ 335:815
    [Google Scholar]
  45. 45.
    Larque E, Pagan A, Prieto MT, Blanco JE, Gil-Sanchez A et al. 2014. Placental fatty acid transfer: a key factor in fetal growth. Ann. Nutr. Metab. 64:247–53
    [Google Scholar]
  46. 46.
    Lattka E, Eggers S, Moeller G, Heim K, Weber M et al. 2010. A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1. J. Lipid Res. 51:182–91
    [Google Scholar]
  47. 47.
    Lattka E, Rzehak P, Szabo E, Jakobik V, Weck M et al. 2011. Genetic variants in the FADS gene cluster are associated with arachidonic acid concentrations of human breast milk at 1.5 and 6 mo postpartum and influence the course of milk dodecanoic, tetracosenoic, and trans-9-octadecenoic acid concentrations over the duration of lactation. Am. J. Clin. Nutr. 93:382–91
    [Google Scholar]
  48. 48.
    Laye S, Nadjar A, Joffre C, Bazinet RP 2018. Anti-inflammatory effects of omega-3 fatty acids in the brain: physiological mechanisms and relevance to pharmacology. Pharmacol. Rev. 70:12–38
    [Google Scholar]
  49. 49.
    Lee S, Lee J, Choi IJ, Kim YW, Ryu KW et al. 2018. Dietary n-3 and n-6 polyunsaturated fatty acids, the FADS gene, and the risk of gastric cancer in a Korean population. Sci. Rep. 8:3823
    [Google Scholar]
  50. 50.
    Lemaitre RN, Tanaka T, Tang W, Manichaikul A, Foy M et al. 2011. Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium. PLOS Genet 7:e1002193
    [Google Scholar]
  51. 51.
    Martinelli N, Girelli D, Malerba G, Guarini P, Illig T et al. 2008. 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. 88:941–49
    [Google Scholar]
  52. 52.
    Mathias RA, Fu W, Akey JM, Ainsworth HC, Torgerson DG et al. 2012. Adaptive evolution of the FADS gene cluster within Africa. PLOS ONE 7:e44926
    [Google Scholar]
  53. 53.
    Mathieson S, Mathieson I. 2018. FADS1 and the timing of human adaptation to agriculture. Mol. Biol. Evol. 35:2957–70
    [Google Scholar]
  54. 54.
    Meldrum SJ, Li Y, Zhang G, Heaton AEM, D'Vaz N et al. 2018. Can polymorphisms in the fatty acid desaturase (FADS) gene cluster alter the effects of fish oil supplementation on plasma and erythrocyte fatty acid profiles? An exploratory study. Eur. J. Nutr. 57:2583–94
    [Google Scholar]
  55. 55.
    Miles EA, Calder PC. 2017. Can early omega-3 fatty acid exposure reduce risk of childhood allergic disease?. Nutrients 9:784
    [Google Scholar]
  56. 56.
    Mohajeri S, Newman SA. 2014. Review of evidence for dietary influences on atopic dermatitis. Skin Ther. Lett. 19:5–7
    [Google Scholar]
  57. 57.
    Molto-Puigmarti C, Plat J, Mensink RP, Muller A, Jansen E et al. 2010. FADS1 FADS2 gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk. Am. J. Clin. Nutr. 91:1368–76
    [Google Scholar]
  58. 58.
    Morales E, Bustamante M, Gonzalez JR, Guxens M, Torrent M et al. 2011. Genetic variants of the FADS gene cluster and ELOVL gene family, colostrums LC-PUFA levels, breastfeeding, and child cognition. PLOS ONE 6:e17181
    [Google Scholar]
  59. 59.
    O'Neill CM, Minihane AM. 2017. The impact of fatty acid desaturase genotype on fatty acid status and cardiovascular health in adults. Proc. Nutr. Soc. 76:64–75
    [Google Scholar]
  60. 60.
    Polokowski AR, Shakil H, Carmichael CL, Reigada LC 2019. Omega-3 fatty acids and anxiety: a systematic review of the possible mechanisms at play. Nutr. Neurosci. In press. https://doi.org/10.1080/1028415X.2018.1525092
    [Crossref] [Google Scholar]
  61. 61.
    Prieto-Sánchez MT, Ruiz-Palacios M, Blanco-Carnero JE, Pagan A, Hellmuth C et al. 2017. Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes. Clin. Nutr. 36:513–21
    [Google Scholar]
  62. 62.
    Ramakrishnan U, Stein AD, Parra-Cabrera S, Wang M, Imhoff-Kunsch B et al. 2010. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr. Bull. 31:Suppl. 2S108–16
    [Google Scholar]
  63. 63.
    Rzehak P, Thijs C, Standl M, Mommers M, Glaser C et al. 2010. Variants of the FADS1 FADS2 gene cluster, blood levels of polyunsaturated fatty acids and eczema in children within the first 2 years of life. PLOS ONE 5:e13261
    [Google Scholar]
  64. 64.
    Schaeffer L, Gohlke H, Muller M, Heid IM, Palmer LJ et al. 2006. 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. 15:1745–56
    [Google Scholar]
  65. 65.
    Schuchardt JP, Kobe T, Witte V, Willers J, Gingrich A et al. 2016. Genetic variants of the FADS gene cluster are associated with erythrocyte membrane LC PUFA levels in patients with mild cognitive impairment. J. Nutr. Health Aging 20:611–20
    [Google Scholar]
  66. 66.
    Shaikh SR, Kinnun JJ, Leng X, Williams JA, Wassall SR 2015. How polyunsaturated fatty acids modify molecular organization in membranes: insight from NMR studies of model systems. Biochim. Biophys. Acta Biomembr. 1848:211–19
    [Google Scholar]
  67. 67.
    Shulkin M, Pimpin L, Bellinger D, Kranz S, Fawzi W et al. 2018. n-3 fatty acid supplementation in mothers, preterm infants, and term infants and childhood psychomotor and visual development: a systematic review and meta-analysis. J. Nutr. 148:409–18
    [Google Scholar]
  68. 68.
    Singmann P, Rzehak P, Berdel D, Wichmann HE, Heinrich J 2010. No association between FADS polymorphisms and atopic diseases in children from the GINI and LISA birth cohorts. Allergy 65:1627–29
    [Google Scholar]
  69. 69.
    Smith GD, Timpson N, Ebrahim S 2008. Strengthening causal inference in cardiovascular epidemiology through Mendelian randomization. Ann. Med. 40:524–41
    [Google Scholar]
  70. 70.
    Smith JP, Forrester R. 2017. Maternal time use and nurturing: analysis of the association between breastfeeding practice and time spent interacting with baby. Breastfeed. Med. 12:269–78
    [Google Scholar]
  71. 71.
    Sprecher H. 2000. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1486:219–31
    [Google Scholar]
  72. 72.
    Standl M, Lattka E, Stach B, Koletzko S, Bauer CP et al. 2012. FADS1 FADS2 gene cluster, PUFA intake and blood lipids in children: results from the GINIplus and LISAplus studies. PLOS ONE 7:e37780
    [Google Scholar]
  73. 73.
    Standl M, Sausenthaler S, Lattka E, Koletzko S, Bauer CP et al. 2011. FADS gene variants modulate the effect of dietary fatty acid intake on allergic diseases in children. Clin. Exp. Allergy 41:1757–66
    [Google Scholar]
  74. 74.
    Standl M, Sausenthaler S, Lattka E, Koletzko S, Bauer CP et al. 2012. FADS gene cluster modulates the effect of breastfeeding on asthma: results from the GINIplus and LISAplus studies. Allergy 67:83–90
    [Google Scholar]
  75. 75.
    Steer CD, Davey Smith G, Emmett PM, Hibbeln JR, Golding J 2010. FADS2 polymorphisms modify the effect of breastfeeding on child IQ. PLOS ONE 5:e11570
    [Google Scholar]
  76. 76.
    Steer CD, Lattka E, Koletzko B, Golding J, Hibbeln JR 2013. Maternal fatty acids in pregnancy, FADS polymorphisms, and child intelligence quotient at 8 y of age. Am. J. Clin. Nutr. 98:1575–82
    [Google Scholar]
  77. 77.
    Sullivan EM, Pennington ER, Green WD, Beck MA, Brown DA, Shaikh SR 2018. Mechanisms by which dietary fatty acids regulate mitochondrial structure–function in health and disease. Adv. Nutr. 9:247–62
    [Google Scholar]
  78. 78.
    Tanjung C, Rzehak P, Sudoyo H, Mansyur M, Munasir Z et al. 2018. The effect of fatty acid desaturase gene polymorphisms on long chain polyunsaturated fatty acid composition in Indonesian infants. Am. J. Clin. Nutr. 108:135–44
    [Google Scholar]
  79. 79.
    Vazquez-Vidal I, Voruganti VS, Hannon BA, Andrade FCD, Aradillas-Garcia C et al. 2018. Serum lipid concentrations and FADS genetic variants in young Mexican college students: the UP-AMIGOS Cohort Study. Lifestyle Genom 11:40–48
    [Google Scholar]
  80. 80.
    Vessby B. 2003. Dietary fat, fatty acid composition in plasma and the metabolic syndrome. Curr. Opin. Lipidol. 14:15–19
    [Google Scholar]
  81. 81.
    Willemsen LEM. 2016. Dietary n-3 long chain polyunsaturated fatty acids in allergy prevention and asthma treatment. Eur. J. Pharmacol. 785:174–86
    [Google Scholar]
  82. 82.
    Ye K, Gao F, Wang D, Bar-Yosef O, Keinan A 2017. Dietary adaptation of FADS genes in Europe varied across time and geography. Nat. Ecol. Evol. 1:0167
    [Google Scholar]
  83. 83.
    Zhang JY, Kothapalli KS, Brenna JT 2016. Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis. Curr. Opin. Clin. Nutr. Metab. Care 19:103–10
    [Google Scholar]
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