Genetics and nutrition


      The understanding of the role of nutrients on DNA stability, repair and on the different gene expression processes recently became more prominent in nutritional science. Nutrients and the genomics interact at two levels. Nutrients can induce gene expression thereby altering individual phenotype. Conversely single nucleotide polymorphisms, in a range of genes important in inflammation and lipid metabolism, alter the bioactivity of important metabolic pathways and mediators and influence the ability of nutrients to interact with them.
      The study on single effects of nutrients on the individual's phenotype as well as the serial analyses of gene expression patterns in response to specific nutrients will help us to understand how metabolic homeostasis is maintained. Considering that there is wide variation in the ability of nutritional factors to modulate the expression of detrimental or protective proteins at an individual level, the concept of diet-medication could be developed in the light of a better understanding of nutrient–gene interactions. In this way, ‘good responders’ and ‘poor responders’ to diet therapy can be identified. Furthermore, as several vitamins participate in DNA protection and genomic stabilisation, diet-linked therapies could become part of cancer prevention and other treatments with relevant consequences for human health.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Subramanian G, Adams M D, Venter J C, Broder S. Implications of the human genome for understanding human biology and medicine. JAMA 2001; 286: 2296–2307

      2. Jousse C, Bruhat A, Ferrara M, Fafournoux P. Evidence for multiple signaling pathways in the regulation of gene expression by amino acids in human cell lines. J Nutr 2000; 130: 1555–1560

      3. Bain P J, LeBlanc-Chaffin R, Chen H, Palii S S, Leach K M, Kilberg M S. The mechanism for transcriptional activation of the human ATA2 transporter gene by amino acid deprivation is different than that for asparagine synthetase. J Nutr 2002; 132: 3023–3029

      4. Schoonjans K, Brendel C, Mangelsdorf D, Auwerx J. Sterols and gene expression: control of affluence. Biochim Biophys Acta 2000; 1529: 114–125

      5. Ames B N. Micronutrientspreventcancer, delay aging. Toxicol Lett 1998; 102–103: 5–18.

      6. Sies H, Stahl W, Sundquist A R. Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. Ann N Y Acad Sci 1992; 669: 7–20

      7. Duthie S J, Ma A, Ross M A, Collins A R. Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Res 1996; 56: 1291–1295

      8. Collins A R, Olmedilla B, Southon S, Granado F, Duthie S J. Serum carotenoids and oxidative DNA damage in human lymphocytes. Carcinogenesis 1998; 19: 2159–2162

      9. Torbergsen A C, Collins A R. Recovery of human lymphocytes from oxidative DNA damage; the apparent enhancement of DNA repair by carotenoids is probably simply an antioxidant effect. Eur J Nutr 2000; 39: 80–85

      10. Peto R, Doll R, Buckley J D, Sporn M B. Can dietary beta-carotene materially reduce human cancer rates? Nature 1981; 290: 201–208

      11. Ziegler R G. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr 1989; 119: 116–122

      12. Hennekens C H, Buring J E, Manson J E et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. New Engl J Med 1996; 334: 1145–1149

      13. Omenn G S, Goodman G E, Thornquist M D et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New Engl J Med 1996; 334: 1150–1155

      14. The Alpha-Tocopherol BCCPSG. The effect of vitamin E, beta carotene on the incidence of lung cancer and other cancers in male smokers. New Engl J Med 1994; 330: 1029–1035

      15. Bertram J S, Bortkiewicz H. Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells. Am J Clin Nutr 1995; 62: 1327–1336

      16. Obermuller-Jevic U C, Francz P I, Frank J, Flaccus A, Biesalski H K. Enhancement of the UVA induction of haem oxygenase-1 expression by beta-carotene in human skin fibroblasts. FEBS Lett 1999; 460: 212–216

      17. Nagpal S, Chandraratna R A. Vitamin A and regulation of gene expression. Curr Opin Clin Nutr Metab Care 1998; 1: 341–346

      18. Fenech M. Recommended dietary allowances (RDAs) for genomic stability. Mutat Res 2001; 480–481: 51–54

      19. Zingg J M, Jones P A. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis 1997; 18: 869–882

      20. Ames B N. Cancerprevention, diet: help from single nucleotide polymorphisms. Proc Nat Acad Sci USA 1999; 96: 12216–12218

      21. Gulati S, Brody L C, Banerjee R. Posttranscriptional regulation of mammalian methionine synthase by B12. Biochim Biophys Res Commun 1999; 259: 436–442

      22. Jhaveri M S, Wagner C, Trepel J B. Impact of extracellular folate levels on global gene expression. Mol Pharmacol 2001; 60: 1288–1295

      23. Halliwell B. VitaminC, genomic stability. Mutat Res 2001; 475: 29–35

      24. Halliwell B. Vitamin C: poison, prophylactic or panacea? Trends Biochem Sci 1999; 24: 255–259

      25. Rehman A, Collis C S, Yang M et al. The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochim Biophys Res Commun 1998; 246.

      26. Catani M V, Rossi A, Costanzo A et al. Induction of gene expression via activator protein-1 in the ascorbate protection against UV-induced damage. Biochem J 2001; 356: 77–85

      27. Sowers M, Lachance L. Vitamins and arthritis. The roles of vitamins A, C, D, and E. Rheum Dis Clin North Am 1999; 25: 315–332

      28. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999; 69: 842–856

      29. Chatterjee M. Vitamin D, genomic stability. Mutat Res 2001; 475: 69–87

      30. Wang S H, Koenig R J, Giordano T J, Myc A, Thompson N W, Baker J R J. 1 alpha, 25-dihydroxyvitamin D3 up-regulates Bcl-2 expression and protects normal human thyrocytes from programmed cell death. Endocrinology 1999; 140: 1649–1656

      31. Brelvi Z S, Studzinski G P. Inhibition of DNA synthesis by an inducer of differentiation of leukemic cells, 1 alpha, 25 dihydroxy vitamin D3, precedes down regulation of the c-myc gene. J Cell Physiol 1986; 128: 171–179

      32. Kuroki Y, Shiozawa S, Kano J, Chihara K. Competition between c-fos and 1, 25(OH)2 vitamin D3 in the transcriptional control of type I collagen synthesis in MC3T3-E1 osteoblastic cells. J Cell Physiol 1995; 164: 459–464

      33. Li Y C, Kong J, Wei M, Chen Z F, Liu S Q, Cao L P. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002; 110: 229–238

      34. Farach-Carson M C, Xu Y. Microarray detection of gene expression changes induced by 1,25(OH)(2)D(3) and a Ca(2+) influx-activating analog in osteoblastic ROS 17/2.8 cells. Steroids 2002; 67: 467–470

      35. Feki M, Souissi M, Mebazaa A. Vitamin E: structure, metabolism, and functions. Ann Med Interne 2001; 152: 384–391

      36. Claycombe K J, Meydani S N. Vitamin E and genome stability. Mutat Res 2001; 475: 37–44

      37. Brigelius-Flohe R, Kelly F J, Salonen J T, Neuzil J, Zingg J M, Azzi A. The European perspective on vitamin E: current knowledge and future research. Am J Clin Nutr 2002; 76: 703–716

      38. Aratri E, Spycher S E, Breyer I, Azzi A. Modulation of alpha-tropomyosin expression by alpha-tocopherol in rat vascular smooth muscle cells. FEBS Lett 1999; 447: 91–94

      39. Zhao B, Yu W, Qian M et al. Involvement of activator protein-1 (AP-1) in induction of apoptosis by vitamin E succinate in human breast cancer cells. Mol Carcinog 1997; 19: 180–190

      40. Calabrese V, Scapagnini G, Catalano C et al. Regulation of heat shock protein synthesis in human skin fibroblasts in response to oxidative stress: role of vitamin E. Int J Tissue React 2001; 23: 127–135

      41. Li-Weber M, Giaisi M, Treiber M K, Krammer P H. Vitamin E inhibits IL-4 gene expression in peripheral blood T cells. Eur J Immunol 2002; 32: 2401–2408

      42. Ricciarelli R, Maroni P, Ozer N, Zingg J M, Azzi A. Age-dependent increase of collagenase expression can be reduced by alpha-tocopherol via protein kinase C inhibition. Free Rad Biol Med 1999; 27: 729–737

      43. Jefferson L S, Kimball S R. Amino acid regulation of gene expression. J Nutr 2001; 131: 2460–2466

      44. Wang X Z, Lawson B, Brewer J W et al. Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol Cell Biol 1996; 16: 4273–4280

      45. Bruhat A, Jousse C, Wang X Z, Ron D, Ferrara M, Fafournoux P. Amino acid limitation induces expression of CHOP, a CCAAT/enhancer binding protein-related gene, at both transcriptional and post-transcriptional levels. J Biol Chem 1997; 272: 17588–17593

      46. Varga J, Li L, Mauviel A, Jeffrey J, Jimenez S A. l-Tryptophan in supraphysiologic concentrations stimulates collagenase gene expression in human skin fibroblasts. Lab Invest 1994; 70: 183–191

      47. Escher P, Wahli W. Peroxisome proliferator-activated receptors: insight into multiple cellular functions. Mutat Res 2000; 448: 121–138

      48. Berger J, Moller D E. The mechanisms of action of PPARs. Ann Rev Med 2002; 53: 409–435

      49. Motojima K, Passilly P, Peters J M, Gonzalez F J, Latruffe N. Expression of putative fatty acid transporter genes are regulated by peroxisome proliferator-activated receptor alpha and gamma activators in a tissue- and inducer-specific manner. J Biol Chem 1998; 273: 16710–16714

      50. Schoonjans K, Watanabe M, Suzuki H et al. Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. J Biol Chem 1995; 270: 19269–19276

      51. Tugwood J D, Issemann I, Anderson R G, Bundell K R, McPheat W L, Green S. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5’ flanking sequence of the rat acyl CoA oxidase gene. EMBO J 1992; 11: 433–439

      52. Marcus S L, Miyata K S, Zhang B S S, Rachubinski R A, Capone J P. Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression. Proc Nat Acad Sci USA 1993; 90: 5723–5727

      53. Zhang B, Marcus S L, Miyata K S, Subramani S, Capone J P, Rachubinski R A. Characterization of protein-DNA interactions within the peroxisome proliferator-responsive element of the rat hydratase-dehydrogenase gene. J Biol Chem 1993; 268: 12939–12945

      54. Tontonoz P, Hu E, Spiegelman B M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994; 79: 1147–1156

      55. Tontonoz P, Hu E, Devine J, Beale E G, Spiegelman B M. PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol 1995; 15: 351–357

      56. Schoonjans K, Peinado-Onsurbe J, Lefebvre A M et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15: 5336–5348

      57. Kelly L J, Vicario P P, Thompson G M et al. Peroxisome proliferator-activated receptors gamma and alpha mediate in vivo regulation of uncoupling protein (UCP-1, UCP-2, UCP-3) gene expression. Endocrinology 1998; 139: 4920–4927

      58. Hofmann C, Lorenz K, Braithwaite S S et al. Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance. Endocrinology 1994; 134: 264–270

      59. Kallen C B, Lazar M A. Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. Proc Nat Acad Sci USA 1996; 93: 5793–5796

      60. Vaulont S, Vasseur-Cognet M, Kahn A. Glucose regulation of gene transcription. J Biol Chem 2000; 275: 31555–31558

      61. Decaux J F, B.A, Kahn A. Regulation of the expression of the l-type pyruvate kinase gene in adult rat hepatocytes in primary culture. J Biol Chem 1989; 264: 11584–11590

      62. Marie S, Diaz-Guerra M J, Miquerol L, Kahn A, Iynedjian P. The pyruvate kinase gene as a model for studies of glucose-dependent regulation of gene expression in the endocrine pancreatic beta-cell type. J Biol Chem 1993; 268: 23881–23890

      63. Brun T, Roche E, Kim K H, Prentki M. Glucose regulates acetyl-CoA carboxylase gene expression in a pancreatic beta-cell line (INS-1). J Biol Chem 1993; 268: 18905–18911

      64. Foufelle F, Gouhot B, Pegorier J P, Perdereau D, Girard J, Ferre P. Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate. J Biol Chem 1992; 267: 20543–20546

      65. Prip-Buus C, Perdereau D, Foufelle F, Maury J, Ferre P, Girard J. Induction of fatty-acid-synthase gene expression by glucose in primary culture of rat hepatocytes. Dependency upon glucokinase activity. Eur J Biochem 1995; 230: 309–315

      66. Foufelle F, Ferre P, 377–391. BJ. New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J 2002; 366: 377–391

      67. Lockhart D J, Winzeler E A. Genomics, gene expression and DNA arrays. Nature 2000; 405: 827–836

      68. Hirschi K D, Kreps J A, Hirschi K K. Molecular approaches to studying nutrient metabolism and function: an array of possibilities. J Nutr 2001; 131: 1605S–1609S

      69. Blanchard R K, Moore J B, Green C L, Cousins R J. Modulation of intestinal gene expression by dietary zinc status: effectiveness of cDNA arrays for expression profiling of a single nutrient deficiency. Proc Nat Acad Sci USA 2001; 98: 13507–13513

      70. Sachidanandam R, D W, Schmidt S C et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001; 409: 928–933

      71. Ueland P M, Hustad S, Schneede J, Refsum H, Vollset S E. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci 2001; 22: 195–201

      72. Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics 2001; 1: 189–201

      73. Talmud P J, Waterworth D M. In-vivo and in-vitro nutrient–gene interactions. Curr Opin Lipidol 2000; 11: 31–36

      74. Melton D W. The use of gene targeting to develop animal models for human genetic diseases. Biochem Soc Trans 1990; 18: 1035–1039

      75. Carter CP, Howles PN, Hui DY. Genetic variation in cholesterol absorption efficiency among inbred strains of mice. J Nutr 1997; 127: 1344–1348

      76. Howles P N, Carter C P, Hui D Y. Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice. J Biol Chem 1996; 271: 7196–7202

      77. Meiner V L, Cases S, Myers H M et al. Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: evidence suggesting multiple cholesterol esterification enzymes in mammals. Proc Nat Acad Sci USA 1996; 93: 14041–14046