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Diet, genes and disease: implications for nutrition policy

Published online by Cambridge University Press:  07 March 2007

Michael J. Gibney  and
Eileen R. Gibney
Michael J. Gibney*
Affiliation:
Institute of European Food Studies, Department of Clinical Medicine, Trinity College, Dublin, Republic of Ireland
Eileen R. Gibney
Affiliation:
Institute of European Food Studies, Department of Biochemistry, Trinity College, Dublin, Republic of Ireland
*
Corresponding author: Professor M. Gibney, fax +353 1 454 2043, email mgibney@tcd.ie
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Abstract

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There is extensive evidence to show that there is considerable variation in diet and disease patterns in Europe and that many of the dietary patterns are predictive of chronic disease. Increasingly, there is evidence that this dietary effect is mediated by genetic background. The present paper examines the role of polymorphisms within three genes, those responsible for the synthesis of apoE, 5,10-methylenetetrahydrofolate reductase (MTHFR) and PPARγ. There is clear evidence to support the concept that the diet–disease link is moderated by genetic variation. The paper then considers whether this moderating effect will have implications for dietary recommendations. In the formulation of dietary reference values it has long been recognized that these values cannot cover the needs of all individuals. By setting the upper level at the mean value +2 sd, the needs of 97·5% of the population are covered. Setting a hypothetical scenario of a nutrient requirement of 200 mg\d and a polymorphism with an allelic frequency in the general population in the range of 0, 10, 20 and 30% that causes an increased nutrient requirement of 25%, there was no evidence that the traditional approach requires revision. Whilst it is recognized that genetic variability may not influence population goals, genetic variability will have to be taken into account in the clinical nutrition management of disease. To knowingly assign a patient to life-long treatment with a diet that for genetic reasons will have no success is both unethical and uneconomical. Once accepted in clinical nutrition, the diet–gene interaction will filter into the prevention of disease in public health nutrition.

Keywords

DietGenesDiseaseNutrition policy
Type
Symposium on ‘Implications for dietary guidelines of genetic influences on requirements’
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 3 , August 2004 , pp. 491 - 500
Copyright
Copyright © The Nutrition Society 2004

References

Aro, A, Kardinal, AF, Salminen, I, Kark, JD, Riemersma, RA, Delgado-Rodriguez, M. et al. (1995) Adipose tissue isomeric trans fatty acids and risk of myocardial infarction in nine countries: the EURAMIC study. Lancet 345, 273–278.CrossRefGoogle ScholarPubMed
Botto, LD & Yang, Q (2000) 5,10-methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGe review. American Journal of Epidemiology 151, 862–877.CrossRefGoogle Scholar
Cobb, MM & Teitlebaum, H (1994) Determinants of plasma cholesterol responsiveness to diet. British Journal of Nutrition 71, 271–282.Google Scholar
Cobb, MM, Teitlebaum, H, Risch, N, Jekel, J & Ostfeld, A (1992) Influence of dietary fat, apolipoprotein E phenotype, and sex on plasma lipoprotein levels. Circulation 86, 849–857.Google Scholar
Corbo, RM, Scacchi, R, Mureddu, L, Mulas, G, Castrechini, S & Rivasi, AP (1999) Apolipoprotein B, apolipoprotein E and angiotensin converting enzyme polymorphisms in 2 Italian populations at different risk for coronary artery disease and comparison of allele frequencies among European populations. Human Biology 71, 933–945.Google ScholarPubMed
Corridan, B (1995) Fatty acid composition of human tissue in health and disease. PhD Thesis, Trinity College Dublin.Google Scholar
Danesh, J & Lewington, S (1998) Plasma homocysteine and coronary heart disease: systematic review of published epidemiological studies. Journal of Cardiovascular Risk 5, 229–232.CrossRefGoogle ScholarPubMed
de Bree, A, Verschuren, M, Kromhout, D, Kluitjmans, LAJ & Blom, HJ (2002) Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease. Pharmacological Reviews 54, 600–618.CrossRefGoogle ScholarPubMed
de Bree, A, Verschuren, WM, Blom, HJ, Nadeau, M, Trijbels, FJ & Kromhout, D (2003) Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study. Atherosclerosis 166, 369–377.Google Scholar
De Michele, M, Panico, S, Iannuzzi, A, Celentano, E, Ciardullo, AV, Galasso, R, Sacchetti, L, Zarrilli, F, Bond, MG & Rubba, P (2002) Association of obesity and central fat distribution with carotid artery wall thickening in middle-aged women. Stroke 33, 2923–2928.Google Scholar
Department of Health (1991). Dietary Reference Values for Food Energy and Nutrient Requirements for the United Kingdom. Report on Health and Social Subjects no. 41. London: H.M. Stationery Office.Google Scholar
Eichner, JE, Dunn, ST, Perveen, G, Thompson, DM, Stewart, KE & Berrit, CS (2002) Apolipoprotein E polymorphism and cardiovascular disease: a HuGe review. American Journal of Epidemiology 155, 487–495.Google Scholar
Eikelboom, JW, Lonn, E, Genest, J, Hankey, G, Yusuf, S & Genest, J Jr (1999) Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Annals of Internal Medicine 131, 363–375.Google Scholar
Enattah, NS, Sahi, T, Savilahti, E, Terwilliger, JD, Peltonen, L & Jarvela, I (2002) Identification of a variant associated with adult hypolactasia. Nature Genetics 30, 233–237.CrossRefGoogle Scholar
Farrer, LA, Cupples, A, Haines, JL, Hyman, B, Kukull, WA, Mayeux, R, Myers, RH, Pericak-Vance, MA, Risch, N & Van Duijn, CM (1997) Effect of age, sex, and ethnicity on the association between apolipoprotein E genotype and alzheimers disease – a meta analysis. Journal of the American Medical Association 278, 1349–1356.Google Scholar
Fletcher, O & Kessling, AM (1998) MTHFR association with arteriosclerotic vascular disease?. Human Genetics 103, 11–21.Google Scholar
Food and Nutrition Board/Institute of Medicine (2000) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press.Google Scholar
Frosst, P, Blom, HJ, Milos, R, Goyette, P, Sheppard, CA, Matthews, RG, et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation to methylenetetrahydrofolate reductase. Nature Genetics 10, 111–113.CrossRefGoogle ScholarPubMed
Gerdes, LU, Klausen, IC, Sihm, I & Faergeman, O (1992) Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world. Genetic Epidemiology 9, 155–167.CrossRefGoogle Scholar
Gudnason, V, Stansbie, D, Scott, J, Bowron, A, Nicaud, V & Humphries, S (1998) C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. Atherosclerosis 136, 347–354.CrossRefGoogle ScholarPubMed
Harmon, DL, Woodside, JV, Yarnell, JW, McMaster, D, Young, IS, McCrum, EE. et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Quarterly Journal of Medicine 89, 571–577.CrossRefGoogle Scholar
Jacobs, DR, Anderson, JT, Hannan, P, Keys, A & Blackburn, H (1983) Variability in individual serum cholesterol response to diet. Arteriosclerosis 3, 349–356.Google Scholar
Jump, DB & Clarke, SD (1999) Regulation of gene expression by dietary fat. Annual Review of Nutrition 19, 63–90.Google Scholar
Kang, SS, Passen, EL, Ruggie, N, Wong, PW & Sora, H (1993) Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease. Circulation 88, 1463–1469.CrossRefGoogle ScholarPubMed
Katan, MB, Beynen, AC, de Vries, JH & Nobels, A (1986) Existence of a consistent hypo and hyper responders to dietary cholesterol in man. American Journal of Epidemiology 123, 221–234.Google Scholar
Keys, A (1980) Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease. London: Harvard University Press.Google Scholar
Keys, A, Anderson, JT & Grande, F (1957) Prediction of serum-cholesterol responses of man to changes in fats in the diet. Lancet 273, 959–966.Google Scholar
Klerk, M, Verhoef, P, Clarke, R, Blom, HJ & Kok, F (2002) MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta analysis. Journal of the American Medical Association 288, 2023–2032.CrossRefGoogle Scholar
Kluijtmans, LA & Whitehead, AS (2001) Methylenetetrahydrofolate reductase genotypes and predisposition to atherothrombotic disease: evidence that all three MTHFR C677T genotypes confer different levels of risk. European Heart Journal 22, 294–299.Google Scholar
Kluijtmans, LA, Young, IS, Boreham, CA, Murray, L, McMaster, , McNulty, DH, Strain, JJ, McPartlin, J, Scott, JM & Whitehead, AS (2003) Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. Blood 101, 2483–2488.Google Scholar
Kromhout, D (2001) Epidemiology of cardiovascular diseases in Europe. Proceedings of the Nutrition Society 4, 441–457.Google ScholarPubMed
Kromhout, D, Menotti, A, Bloemberg, B, Aravanis, C, Blackburn, H, Buzina, R. et al. (1995) Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: The Seven Countries Study. Preventive Medicine 24, 308–315.Google Scholar
Lahoz, C, Schaefer, EJ, Cupples, LA, Wilson, PW, Levy, D, Osgood, D, Parpos, S, Pedro-Botet, J, Daly, JA & Ordovas, JM (2001) Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study. Atherosclerosis 15, 529–537.Google Scholar
Litynski, P, Loehrer, F, Linder, L, Todesco, L & Fowler, B (2002) Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C→T polymorphism in methylenetetrahydrofolate reductase. European Journal of Clinical Nutrition 32, 662–668.Google ScholarPubMed
Loktinov, A (2003) Common gene polymorphisms and nutrition: emerging links with pathogenesis of multifactorial chronic diseases. Journal of Nutritional Biochemistry 14, 426–451.Google Scholar
Luan, J, Browne, PO, Harding, AH, Halsall, DJ, O'Rahilly, S, Chatterjee, VKK & Wareham, N (2001) Evidence for gene-nutrient interaction at the PPARγ locus. Diabetes 50, 686–689.Google Scholar
McKinley, MC (2000) Nutritional aspects and possible pathological mechanisms of hyperhomocysteinemia: an independent risk factor for vascular disease. Proceedings of the Nutrition Society 59, 221–237.Google Scholar
Mason, LF, McNeill, G & Avenell, A (2003) Genetic variation and the lipid response to dietary intervention: a systematic review. American Journal of Clinical Nutrition 77, 1098–1111.CrossRefGoogle Scholar
Ordovas, JM, Lopez-Miranda, J, Mata, P, Perez-Jimenez, F, Lichtenstein, AH & Schaefer, EJ (1995) Gene-diet interaction in determining plasma lipid response to dietary intervention. Atherosclerosis 118, S11–S27.Google Scholar
Panza, F, Solfizzi, V, Torres, F, Mastroianni, F Del Parigi, A, Colacicco, AM, Basile, AM, Capurso, C, Noya, R & Capurso, A (1999) Decreased frequency of apoliprotein E ɛ4 allele from Northern to Southern Europe in Alzheimer's disease patients and centenarians. Neuroscience Letters 277, 53–56.Google Scholar
Paoloni-Giacobino, A, Grimble, R & Pichard, C (2003) Genetics and nutrition. Clinical Nutrition 22, 429–435.Google Scholar
Riemersma, RA, Wood, DA, Butler, S, Elton, RA, Oliver, M, Salo, M et al. (1986) Linoleic acid content in adipose tissue and coronary heart disease. British Medical Journal 292, 1423–1427.Google Scholar
Sahi, T (1994) Genetics and epidemiology of adult-type hypolactasia. Scandinavian Journal of Gastroenterology 202, Suppl. 7–20.Google Scholar
Sans, S, Kesteloot, H & Kromhout, D (1997) The burden of cardiovascular diseases mortality in Europe. European Heart Journal 18, 1231–1248.Google Scholar
Savolainen, MJ, Rantala, M, Kervinen, K, Jarvi, L, Suvanto, K, Rantala, T & Kesaniemi, YA (1991) Magnitude of dietary effects on plasma cholesterol concentration: role of sex and apolipoprotein E phenotype. Atherosclerosis 86, 145–152.Google Scholar
Schaefer, EJ (2000) Lipoproteins, nutrition and heart disease. American Journal of Clinical Nutrition 75, 191–212.Google Scholar
Schiele, F De Bacquer, D Vincent-Viry, M Beisiegel, U, Ehnholm, C, Evans, A. et al. (2000) Apoliprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project. Atherosclerosis 152, 475–488.Google Scholar
Scriver, CR, Hurtubise, M, Konecki, D, Phommarinh, M, Prevost, L, Erlandsen, H, Stevens, R, Waters, PJ, Sarkissian, C, McDonald, D & Ryan, S (2003) PAHdb: what a locus specific knowledgebase can do. Human Mutation 21, 333–344.Google Scholar
Sheehan, D, Bennett, T & Cashman, K (2000) Apolipoprotein E gene polymorphisms and serum cholesterol in healthy Irish adults: a proposed genetic marker for coronary artery disease risk. Irish Journal of Medical Science 169, 50–54.Google Scholar
Slimani, N, Fahey, M, Welch, AA, Wirfalt, E, Stripp, C, Bergstrom, E. et al. (2002) Diversity of dietary patterns observed in the European Prospective Investigation into Cancer and Nutrition (EPIC) project. Proceedings of the Nutrition Society 5, 1311–1328.Google Scholar
Suk, SH, Sacco, RL, Boden-Albala, B, Cheun, JF, Pittman, JG, Elkind, MS & Paik, MC (2003) Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study. Stroke 34, 1586–1592.Google Scholar
Tanne, D, Haim, M, Goldbourt, U, Boyko, V, Doolman, R, Adler, Y, Brunner, D, Behar, S & Sela, BA (2003) Prospective study of serum homocysteine and risk of ischemic stroke among patients with preexisting coronary heart disease. Stroke 34, 632–636.Google Scholar
Thomas, F, Rudnichi, A, Bacri, AM, Bean, K, Guize, L & Benetos, A (2001) Cardiovascular mortality in hypertensive men according to presence of associated risk factors. Hypertension 37, 1256–1261.Google Scholar
Tikkanen, MJ, Huttunen, JK, Enholm, C & Pietinen, P (1990) Apolipoprotein e4 homozygosity predispose to serum cholesterol elevation during high fat diet. Arteriosclerosis 10, 285–288.Google Scholar
Van der Put, NM, Gabreels, F, Stevens, EM, Smeitink, JA, Trijbels, FJ, Eskes, TK, van den Heuvel, LP & Blom, HJ (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. American Journal of Human Genetics 62, 1044–1051.CrossRefGoogle ScholarPubMed
Venn, BJ, Green, TJ, Moser, R & Mann, JI (2003) Comparison of the effect of low dose supplementation with l -5 methyltetrahydrofolate of folic acid on plasma homocysteine: a randomized placebo controlled study. American Journal of Clinical Nutrition 77, 658–662.CrossRefGoogle Scholar
Vincent, S, Plannells, R, Defoort, C, Bernard, MC, Gerber, M, Prudhomme, J, Vague, P & Lairon, D (2002) Genetic polymorphisms and lipoprotein responses to diets. Proceedings of the Nutrition Society 61, 427–434.Google Scholar
Waters, PJ (2003) How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression. Human Mutations 21, 357–369.Google Scholar
Weggemans, RM, Zock, PL, Ordovas, JM, Ramos-Galluzzi, J & Katan, MB (2001) Genetic polymorphisms and lipid response to dietary changes in humans. European Journal of Clinical Investigation 31, 950–957.Google Scholar
Wilson, PW, D'Agostino, RB, Sullivan, L, Parise, H & Kannel, WB (2002) Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Archives of Internal Medicine 162, 1867–1872.Google Scholar
Ye, SQ & Kwiterovich, PO (2000) Influence of genetic polymorphisms on responsiveness to dietary fat and cholesterol. American Journal of Clinical Nutrition 72, Suppl. 1275S–1284S.Google Scholar
Yen, CJ, Beamer, BA, Negri, C, Silver, K, Brown, KA, Yarnall, DP, Burns, DK, Roth, J & Shuldiner, AR (1997) Molecular scanning of the human peroxisome proliferator activated receptorγ (hPPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ 2 missense mutation. Biochemical and Biophysical Research Communications 241, 270–274.Google Scholar