Abstract
Because they have recognisable mendelian subsets, multifactorial polygenic diseases like hypertension, coronary artery disease (CAD), diabetes, and cancer all have varying rates of prevalence and mortality. These rates are dependent on the genetic susceptibility of an individual as well as the environmental factors that contribute to their development. Alterations in diet and lifestyle that take place suddenly have the potential to affect the heredity of variant phenotypes whose expression is contingent on the consumption of nutraceutical or functional food supplements. It is feasible to identify the way in which particular nutraceuticals interact with the genetic code that is possessed by all nucleated cells. There is evidence to suggest that South Asians have a higher risk of developing coronary artery disease (CAD), diabetic mellitus, central obesity, and insulin resistance at a younger age. This elevated risk may be the result of an interplay between genes and the nutritional environment. It would suggest that these populations have a genetic propensity, and there may be an interplay between their internal nutritional state and the elements in their surroundings. A higher consumption of refined starches and sugar leads to an increase in the production of free fatty acids (FFA), as well as an increase in the amount of nuclear factor-kB (NF-kB), a transcriptional factor that regulates the activity of at least 125 genes, the majority of which are pro-inflammatory. Taking in glucose also leads to an increase in the levels of two other pro-inflammatory transcription factors: activating protein-1 (AP-1) and early growth response protein-1 (Egr-1). The activating protein-1 (AP-1) transcription factor is responsible for regulating the transcription of matrix metal-proteinases, while the early growth response protein-1 (Egr-1) transcription factor modulates the transcription of tissue factor and plasminogen activator inhibitor-1. Foods that have been refined and mixed together trigger the activation of the nuclear factor kappa B pathway, which is related with the production of free radicals by mononuclear cells. At least two of the most important transcription factors that contribute to inflammation, NF-kB and AP-1, can be activated by the super oxide anion. A high consumption of linoleic acid, saturated fat, trans fat, refined starches and sugars can lead to an increase in the production of free radicals as well as activation of the nuclear factor kappa B, which in turn causes rapid expression of genes involved in inflammation. It is likely that some nutraceuticals, such as antioxidants, micronutrients, minerals, vitamins, coenzyme Q10, and w-3 fatty acids, could block the synthesis of super oxide and decrease NF-kB in addition to AP-1 and Egr-1, which would then result in the inhibition of phenotypic manifestations. It is common knowledge that genes play a significant role in determining enzymes, receptors, cofactors, and structural components that are involved in the regulation of blood pressure, the metabolism of lipids and lipoproteins, as well as inflammatory and coagulation factors that are involved in the process of determining an individual's risk for vascular diseases and diabetes. Nutraceuticals and slowly digested wild foods that are rich in micronutrients and antioxidants appear to have the potential to mute these phenotypic expressions by targeting small sequence changes known as single nucleotide polymorphisms.
Keywords:
:Single nucleotide polymorphism, chromosome variant, proteome, transcription factor, epigenetics.
References
[1] Ander BP, Hurtado C, Raposo CS, et al. Differential sensitivities of the NCX1. 1 and NCX1. 3 isoforms of the Na+-Ca2+ exchanger to á-linolenic acid. Cardiovasc Res 2007; 73: 395-403.
[2] Aubert J, Champigny O, Saint-Marc P, et al. Upregulation of UCP- 2 gene expression by PPAR agonists in preadipose and adipose cells. Biochem Biophys Res Commun 1997; 238: 606-11.
[3] Bensatti P, Peluso G, Nicolai R, Calvani M. Polyunsaturated fatty acids: biochemical, nutritional and epigenetic properties. J Am Coll Nutr 2004; 23: 281-302.
[4] Berdanier CD, Hargrove JL. Nutrition and Gene Expression. Boca Raton Press: CRC, USA 1993; pp. 10-20.
[5] Clarke SD, Jump DB. Fatty acid regulation of gene expression; a unique role for polyunsaturated fats. In: Berdanier CD, Hargrove JL, Eds. Nutrition and Gene Expression. Boca Raton, FL: CRC Re- views 1992; pp. 227-45.
[6] Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK. A high-resolution survey of deletion polymorphism in the human genome. Nat Genet 2006; 38: 75-81.
[7] De Urquiza AM, Liu S, Sjoberg M, et al. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 2000; 290: 2140-44.
[8] DeBose-Boyd RA, Ou J, Goldstein JL, Brown MS. Expression of sterol regulatory element-binding protein 1c (SREBP-1c) mRNA in rat hepatoma cells requires endogenous LXR ligands. Proc Natl Acad Sci USA 2001; 98: 1477-82.
[9] DeMeester F. Wild-type land-based foods in health promotion and disease prevention: the LDL-CC: HDL-CC model. In: DeMeester F, Watson FF, Eds. Wild Type Foods in Health Promotion and Disease Prevention. Humana Press: NJ 2008; pp. 3-20.
[10] Desvergne B, Wahil W. Peroxisome proliferator -activated recep- tors: nuclear control of metabolism. Endocr Rev 1999; 20: 649-88.
[11] Dolgin E, Keegan K, Allada R. Unlocking the clock. Science 2008; 22: 27.
[12] Doria A, Wojcik J, Xu R, et al. Poor glycemic control modifies 9p21 variant coronary artery disease risk association. JAMA 2008; 300: 2389-97.
[13] DuplusE, Glorian M, Forest C. Fatty acids regulation of gene tran- scription. J Biol Chem 2000; 275: 30749-52.
[14] Fung TT, Chiuve SE, McCullough ML, Rexrode KM, Logroscino G, Hu FB. Adherance to DASH- style diet and risk of coronary heart disease and stroke in women. Arch Intern Med 2008; 168: 713-20.
[15] Guerre-Millo M, Gervois P, Raspe E, et al. Peroxisome proliferator -activated improve insulin sensitivity and reduce adiposity. J Biol Chem 2000; 275: 16638-42.
[16] Hannah VC, Ou J, Luong A, Goldstein JL, Brown MS. Unsatu- rated fatty acids down-regulate SREBP isoforms 1a and 1c by two mechanisms in HEK-293 cells. J Biol Chem 2001; 276: 4365- 72.
[17] Harper CR, Jacobson TA. Usefulness of omega-3 fatty acids and the prevention of coronary heart disease. Am J Cardiol 2005; 96: 1521-29.
[18] Harris WS, Reid KJ, Sands SA, Spertus JA. Blood omega-3 and trans fatty acids in middle aged acute coronary syndrome patients. Am J Cardiol 2007; 99: 154-58.
[19] Hertz R, Magenheim J, Berman I, Bar-Tana J. Fatty acid -CoA esters are ligands of hepatic nuclear factor-4. Nature 1998; 392: 512-6.
[20] Hertz R, Magenheim J, Berman I, Bar-Tana J. Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4alpha. Nature 1997; 392: 512-6.
[21] Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006; 440: 944-8.
[22] Isles AR, Wilkilson LS. Epigenetics: what is it and why it is impor- tant to mental diseases. BMJ 2008; 85: 35-45.
[23] Jiang Z, Sim JS. Consumption of polyunsaturated fatty acid eggs and changes in plasma lipids of human subjects. Nutrition 2003; 9: 513-8.
[24] Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007; 128: 683-92.
[25] Juge-Aubry CE, Gorla-Bajsczak A, Pernin A, et al. Peroxisome proliferator-activated receptor mediates cross-talk with thyroid hormone receptor by competition for retinoid X receptor. Possible role of a leucine zipper-like heptad repeat. J Biol Chem 1995; 270: 18117-22.
[26] Jump DB, Clarke SD, MacDougald OA, Thelen A. Polyunsaturated fatty acids inhibit S14 gene transcription in rat liver and cultured hepatocytes. Proc Natl Acad Sci USA 1993; 90: 8454-8.
[27] Jump DB, Clarke SD, Thelen AT, Liimatta M. Coordinate regula- tion of glycolytic and lipogenic gene expression by polyunsaturated fatty acid. J Lipid Res 1994; 35: 1076-84.
[28] Jump DB, Clarke SD, Theten A, Liimatta M, Ren B, Badin M. Dietary polyunsaturated regulation of gene transcription. Prog Lipid Res 1996; 35: 227-41.
[29] Kang JX, Wank J, Wu L, Kang ZB. Fat 1 mice convert n-6 to n-3 fatty acids. Nature 2004; 427: 304.
[30] Katcher HI, Legro RS, Kunselman AR, et al. The effects of whole grain- enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am J Clin Nutr 2008; 87: 79-90.
[31] Kidd JM, Cooper GM, Donahue WF, et al. Mapping and sequenc- ing of structural variation from eight human genomes. Nature 2008; 453: 56-64.
[32] Kidweel WR. Fatty acid growth requirements of normal and neo- plastic mammary epithelium. Prog Clin Biol Res 1986; 222: 699- 707.
[33] Kim HJ, Takahashi M, Ezaki O. Fish oil feeding decreases mature Streol Regulatory Element-Binding Protein 1 (SREBP-1) by down- regulation of SREBP-1c mRNA in mouse liver. J Biol Chem 1999; 274: 25892-8.
[34] Koide M, Kawahara Y, Tsuda T, Nakayama I, Yokoyama M. Ex- pression of nitric oxide synthase by cytokines in vascular smooth muscle cells. Hypertension 1994; 23 (Suppl 1): 145-48.
[35] Lacoix FCM, De Meester F. The return to wild types fats in the diet. Br Nutr Found Bull 2007; 32: 168-72.
[36] Lai L, Kang JX, Li R, et al. Generation of cloned transgenic pigs rich in n-3 fatty acids. Nat Biotechnol 2006; 4: 433-36.
[37] Lambe KG, Tugwood JD. A human peroxisome-proliferator - activated receptor -gamma is activated by inducers of adipogenesis, including thiazolidinedione drug. Eur J Biochem 1996; 239: 83- 98.
[38] Levy S, Sutton G, Ng PC, et al. The diploid genome sequence of an individual human. PLoS Biol 2007; 5: e254.
[39] Liimatta M, Towle HC, Clarke SD, Jump DB. Dietary polyunsatu- rated Fatty acids interfere with the insulin/glucose activation of L- type pyruvate kinase gene transcription. Mol Endocrinol 1999; 8: 1147-53.
[40] Mascaro C, Acosta E, Ortiz JA, Marrero PF, Hegardt FG, Haro D. Control of human muscle -type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. J Biol Chem 1998; 273: 8560-63.
[41] Masuzaki H, Paterson J, Shinayama H, et al. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001; 294: 2166-70.
[42] Mater MK, Thelen AP, Pan DA, Jump DB. Sterol Response Ele- ment-binding Protein 1c (SREBP 1c) is involved in the poly- unsaturated fatty acid suppression of Hepatic S14 Gene Transcrip- tion. J Biol Chem 1999; 274: 32725-32.
[43] McCarroll SA, Hadnott TN, Perry GH, et al. Common deletion polymorphisms in the human genome. Nat Genet 2006; 38: 86-92.
[44] Miller CC, Ziboh VA. Induction of epidermal hyperproliferation by topical n-3 polyunsaturated fatty acids on guinea pig skin linked to decreased levels of 13-hydroxyoctadecadienoic acid (13-HODE). J Invest Dermatol 1990; 94: 353-8.
[45] Mills RE, Luttig CT, Larkins CE, et al. An initial map of insertion and deletion (INDEL) variation in the human genome. Genome Res 2006; 16: 1182-90.
[46] Mozaffarian D, Geelan A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans, a metaanaly- sis of randomized, controlled trials. Circulation 2005; 112: 1945- 52.
[47] Ohashi K, Ouchi N, Kihara S, et al. Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery dis- ease. J Am Coll Cardiol 2004; 43: 1195-200.
[48] Osborne TF. Sterol Regulatory Element -Binding Proteins (SREBPs): Key regulators of nutritional homeostasis and insulin action. J Biol Chem 2000; 275: 32379-82.
[49] Ou J, Tu H, Shan B, et al. Unsaturated fatty acids inhibit transcrip- tion of the sterol regulatory element-binding protein-1c (SREBP- 1c) gene by antagonizing ligand -dependent activation of theLXR. Proc Natl Acad Sci USA 2000; 98: 6027-32.
[50] Power GW, Newsholme EA. Dietary fatty acids influence the ac- tivity and metabolic control of mitochondrial carnitine palmitoyi- transferase I in rat heart and sheletal muscle. J Nutr 1997; 127: 2142-50.
[51] Redon R, Ishikawa S, Fitch KR, et al. Global variation in copy number in the human genome. Nature 2006; 444: 444-54.
[52] Ren B, Thelen AP, Peters JM, Gonzalez FJ, Jump DB. Polyunsatu- rated fatty acid suppression of hepatic fatty acid synthase and S14 gene expression dose not require peroxisome proliferator-activated receptor alfa. J Biol Chem 1997; 272: 26827-32.
[53] Rodenhiser D, Mann M. Epigenetics, and human disease: translat- ing basic biology in to clinical applications. Can Med Assoc J 2006; 174: 341-8.
[54] Rodriguez JC, Gil-Gomez B, Hegradt FG, Haro D. Peroxisome proliferator -activated receptor mediates induction of the mito- chondrial 3-hydroxy-3-methylglutary -CoA synthase gene by fatty acids, J Biol Chem 1994; 269: 18767-72.
[55] Schulze JJ, Lundmark J, Garle M, Skilving I, Ekström L, Rane A. Doping test results dependent on genotype of UGT2B17, the major enzyme for testosterone glucuronidation. J Clin Endocrinol Metab 2008; 93(7): 2500-6.
[56] Scriver CR. Nutrient gene interactions: the gene is not the disease and viceversa. Am J Clin Nutr 1988; 48: 1505-9.
[57] Singh RB, De Meester F. How clock genes influence heart attack rate in the morning? Response letter to editor. Science (online) 2008; 22: 27.
[58] Singh RB, Niaz MA, Kartik C. Can omega -3 fatty acids provide myocardial protection by decreasing infarct size and inhibiting atherothrombosis? Eur Heart J 2001; 3(Suppl): D62-D69.
[59] Singh RB, Niaz MA. Genetic variation and nutrition, in relation to coronary artery disease. J Assoc Phys India 1999; 47: 1185-90.
[60] Singh RB, Singh V, Kulshrestha SK, et al. Social class and all-cause mortality in an urban population of North India. Acta Cardiol 2005; 60: 611-7.
[61] Storlien L, Hulbert AJ, Else PL. Polyunsaturated fatty acids, mem- berane function and metabolic diseases such as diabetes and obe- sity. Curr Opin Clin Nutr Metab Care 1998; 1: 559-63.
[62] Sumbalova Z, Kucharaska J, Kasparova S, et al. Brain energy metabolism in experimental chronic diabetes: effect of long-term administration of coenzyme Q10 and w-3 polyunsaturated fatty ac- ids. Biologia 2005; 11: 1-13.
[63] Takada R, Saitoh M, Mori T. Dietary gamma-linolenic acid en- riched oil reduces body fat content and induces liver enzyme activi- ties relating to fatty acid beta-oxidation in rats. J Nutr 1994; 124: 469-74.
[64] Trojer P, Reinberg D. Histone, lysine, demethylases and their im- pact on epigenetics. Cell 2006; 125: 213-7.
[65] Ulrev CL, Liu L, Andrews LG, Tollefsbol TO. The impact of metabolism on DNA and methylation. Hum Mol Genet 2005; 14 (Suppl 1): 139-47.
[66] Van der Kils FR, Schmidt ED, Van Beeren HC, Wiersinga WM. Competitive inhibition of T3 binding to alpha 1 and beta 1 thyrroid hormone receptors by fatty acids. Biochem Biophys Res Commun 1991; 179: 1011-6.
[67] Varanasi U, Chu R, Huang Q, Castellon R, Yeldandi AV, Reddy JK. Identification of a peroxisome proliferator-responsive element upstream of the human peroxisomal fatty acyl CoA oxidase gene. J Biol Chem 1996; 271: 2147-55.
[68] Xu J, Nakamura MT, Cho HP, Clarke S. Sterol Regulatory Element Binding Protein-1 expression is suppressed by dietary polyunsatu- rated fatty acids. J Biol Chem 1999; 274: 23577-83.
[69] Ye JM, Doyle PJ, Iglesias MA, Watson DG, Cooney GJ, Kraegen EWW. Peroxisome proliferator-activated receptor (PPAR)- alpha activation lowers muscle lipid and improves insulin sensitivity in high fat-fed rats: comparison with PPAR-gamma activation. Diabetes 2001; 50: 411-7.
[70] Zarranga IGE, Schwartz ER. Impact of dietary patterns and inter- ventions on cardiovascular health. Circulation 2006; 114: 961-73.
[71] Zhang C, Rexrode KM, Van Dam RM, Li TY, Hu FB. Abdominal obesity and the risk of all cause, cardiovascular and cancer mortal- ity. Sixteen years of follow-up in US women. Circulation 2008; 117(13): 1624-6.
