Current Atherosclerosis Reports

, Volume 1, Issue 1, pp 16–23

Treatment of dyslipidemia: Genetic interactions with diet and drug therapy

  • Jose M. Ordovas
  • Ernst J. Schaefer
Article

Abstract

Coronary heart disease (CHD) is multifactorial, and its manifestation is determined by multiple gene loci and their interaction with a cohort of environmental factors. Variation at several candidate gene loci has already been shown to have a significant effect over the spectrum of plasma lipid levels observed in the population. Moreover, some variants are known to influence the interindividual variability in response to dietary and pharmacologic interventions aimed to reduce atherogenic lipoproteins. The continuous progress in this area of research is getting us closer to the development of genetic screening panels that will allow a more precise assessment of individual CHD risk and response to therapeutic interventions.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ordovas JM, Schaefer EJ: Genes, variation of cholesterol and fat intake and serum lipids. Curr Opin Lipidol 1999, 10:15–22.PubMedCrossRefGoogle Scholar
  2. 2.
    Ordovas JM, Lopez-Miranda J, Perez-Jimenez F, et al.: Effect of apolipoprotein E and A-IV phenotypes on the low density lipoprotein response to HMG CoA reductase inhibitor therapy. Atherosclerosis 1995, 113:157–166.PubMedCrossRefGoogle Scholar
  3. 3.
    Schaefer EJ, Lamon-Fava S, Ausman LM, et al.: Individual variability in lipoprotein cholesterol response to national cholesterol education program step 2 diets. Am J Clin Nutr 1997, 65:823–830.PubMedGoogle Scholar
  4. 4.
    Tall A, Welch C, Applebaum-Bowden D, Wassef M.: Interaction of diet and genes in atherogenesis. Report of an NHLBI working group. Arterioscler Thromb Vasc Biol 1997, 17:3326–3331.PubMedGoogle Scholar
  5. 5.
    Carmena R, Roederer G, Mailloux H, et al.: The response to lovastatin treatment in patients with heterozygous familial hypercholesterolemia is modulated by apolipoprotein E polymorphism. Metabolism 1993, 42:895–901.PubMedCrossRefGoogle Scholar
  6. 6.
    Nemeth A, Szakmary KA, Kramer J, et al.: Apolipoprotein E and complement C3 polymorphism and their role in the response to gemfibrozil and low fat low cholesterol therapy. Eur J Clin Chem Clin Biochem 1995, 33:799–804.PubMedGoogle Scholar
  7. 7.
    Nestel P, Simons L, Barter P, et al.: A comparative study of the efficacy of simvastatin and gemfibrozil in combined hyperlipoproteinemia: prediction of response by baseline lipids, apoE genotype, lipoprotein(a) and insulin. Atherosclerosis 1997, 129:231–239PubMedCrossRefGoogle Scholar
  8. 8.
    Connor WE, Connor SL: Should a low-fat, high-carbohydrate diet be recommended for everyone? The case for a low-fat, high-carbohydrate diet. N Engl J Med 1997, 337:562–563; discussion 566–567.PubMedCrossRefGoogle Scholar
  9. 9.
    Katan MB, Grundy SM, Willett WC: Should a low-fat, high-carbohydrate diet be recommended for everyone? Beyond low-fat diets. N Engl J Med 1997, 337:563–566; discussion 566–567.PubMedGoogle Scholar
  10. 10.
    Rudel LL: Low-fat diets [abstract]. N Engl J Med 1998, 338:128.PubMedGoogle Scholar
  11. 11.
    Strain GW: Low-fat diets. N Engl J Med 1998, 338:128.PubMedCrossRefGoogle Scholar
  12. 12.
    Thompson PD: More on low-fat diets. N Engl J Med 1998, 338:1623–1624.PubMedCrossRefGoogle Scholar
  13. 13.
    Grundy SM: What is the desirable ratio of saturated, polyunsaturated, and monounsaturated fatty acids in the diet? Am J Clin Nutr 1997, 66:988S-990S.PubMedGoogle Scholar
  14. 14.
    Oliver MF: It is more important to increase the intake of unsaturated fats than to decrease the intake of saturated fats: evidence from clinical trials relating to ischemic heart disease. Am J Clin Nutr 1997, 66:980S-986S.PubMedGoogle Scholar
  15. 15.
    Stamler J, Greenland P, Van Horn L, Grundy SM: Dietary cholesterol, serum cholesterol, and risks of cardiovascular and non-cardiovascular diseases. Am J Clin Nutr 1998, 67: 488–492.PubMedGoogle Scholar
  16. 16.
    Lopez-Miranda J, Ordovas JM, Espino A, et al.: Influence of mutation in human apolipoprotein A-1 gene promoter on plasma LDL cholesterol response to dietary fat. Lancet, 1994, 343:1246–1249.PubMedCrossRefGoogle Scholar
  17. 17.
    Mata P, Lopez-Miranda J, Pocovi M, et al.: Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation. Atherosclerosis 1998, 137:367–376.PubMedCrossRefGoogle Scholar
  18. 18.
    Carmena-Ramon RF, Ordovas JM, Ascaso JF, et al.: Influence of genetic variation at the apoA-I gene locus on lipid levels and response to diet in familial hypercholesterolemia. Atherosclerosis 1998, 139:107–113.PubMedCrossRefGoogle Scholar
  19. 19.
    Meng QH, Pajukanta P, Valsta L, et al.: Influence of apolipoprotein A-1 promoter polymorphism on lipid levels and responses to dietary change in Finnish adults. J Intern Med 1997, 241:373–378.PubMedCrossRefGoogle Scholar
  20. 20.
    Ordovas JM, Cassidy DK, Civeira F, et al.: Familial apolipoprotein A-I, C-III and A-IV deficiency and premature atherosclerosis due to deletion of a gene complex on chromosome 11. J Biol Chem 1989, 264:16339–16342.PubMedGoogle Scholar
  21. 21.
    Mata P, Ordovas JM, Lopez-Miranda J, et al.: ApoA-IV phenotype affects diet-induced plasma LDL cholesterol lowering. Arterioscler Thromb 1994, 14:884–891.PubMedGoogle Scholar
  22. 22.
    McCombs RJ, Marcadis DE, Ellis J, Weinberg RB: Attenuated hypercholesterolemic response to a high-cholesterol diet in subjects heterozygous for the apolipoprotein A-IV-2 allele. N Engl J Med 1994, 331:706–710.PubMedCrossRefGoogle Scholar
  23. 23.
    Carmena-Ramon RF, Ascaso JF, Real JT, et al.: Rom Genetic variation at the ApoA-IV gene locus and response to diet in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 1998, 18:1266–1274.PubMedGoogle Scholar
  24. 24.
    Jansen S, Lopez-Miranda J, Ordovas JM, et al.: Effect of 360His mutation in apolipoprotein A-IV on plasma HDL-cholesterol response to dietary fat. J Lipid Res 1997, 38:1995–2002.PubMedGoogle Scholar
  25. 25.
    Fisher RM, Burke H, Nicaud V, et al.: Effect of variation in the apoA-IV gene on body mass index and fasting and postprandial lipids in the European Atherosclerosis Research Study II. J Lipid Res 1999, 40:287–294.PubMedGoogle Scholar
  26. 26.
    Jansen S, Lopez-Miranda J, Salas J, et al.: Effect of 347-serine mutation in apoprotein A-IV on plasma LDL cholesterol response to dietary fat. Arterioscler, Thromb Vasc Biol 1997, 17:1532–1538.Google Scholar
  27. 27.
    Dallongeville J, Fruchart JC: Postprandial dyslipidemia: a risk factor for coronary heart disease. Annal Nutr & Metab 1998, 2:1–11.CrossRefGoogle Scholar
  28. 28.
    Lopez-Miranda J, Ordovas JM, Ostos MA, et al.: Dietary fat clearance in normal subjects is modulated by genetic variation at the apolipoprotein B gene locus. Arterioscler Thromb Vasc Biol 1997, 17:1765–1773.PubMedGoogle Scholar
  29. 29.
    Lopez-Miranda J, Jansen S, Ordovas JM, et al.: Influence of the SstI polymorphism at the apolipoprotein C-III gene locus on the plasma low-density-lipoprotein-cholesterol response to dietary monounsaturated fat. Am J Clin Nutr 1997, 66: 97–103.PubMedGoogle Scholar
  30. 30.
    Lefevre M, Ginsberg HN, Kris-Etherton PM, et al.: ApoE genotype does not predict lipid response to changes in dietary saturated fatty acids in a heterogeneous normolipidemic population. The DELTA Research Group. Dietary Effects on Lipoproteins and Thrombogenic Activity. Arterioscler Thromb Vascr Biol 1997, 17:2914–2923.Google Scholar
  31. 31.
    Sarkkinen E, Korhonen M, Erkkila A, et al.: Effect of apolipoprotein E polymorphism on serum lipid response to the separate modification of dietary fat and dietary cholesterol. Am J Clin Nutr 1998, 68:1215–1222.PubMedGoogle Scholar
  32. 32.
    Pasagian-Macaulay A, Aston CE, Ferrell RE, et al.: A dietary and behavioral intervention designed to lower coronary heart disease. Risk factors are unaffected by variation at the APOE gene locus. Atherosclerosis 1997, 132:221–227.PubMedCrossRefGoogle Scholar
  33. 33.
    Dixon LB, Shannon BM, Tershakovec AM, et al.: Effects of family history of heart disease, apolipoprotein E phenotype, and lipoprotein(a) on the response of children’s plasma lipids to change in dietary lipids. Am J Clin Nutr 1997, 66:1207–1217.PubMedGoogle Scholar
  34. 34.
    Lehtimaki T, Frankberg-Lakkala H, Solakivi T, et al.: The effect of short-term fasting, apolipoprotein E gene polymorphism, and sex on plasma lipids. Amer J Clin Nutr 1997, 66: 599–605.PubMedGoogle Scholar
  35. 35.
    Wolever TM, Hegele RA, Connelly PW, et al.: Long-term effect of soluble-fiber foods on postprandial fat metabolism in dyslipidemic subjects with apoE3 and apoE4 genotypes. Amer J Clin Nutr 1997, 66:584–590.PubMedGoogle Scholar
  36. 36.
    Yamashita S, Sakai N, Hirano K, et al.: Molecular genetics of plasma cholesteryl ester transfer protein. Curr Opin Lipidol 1997, 8:101–110.PubMedCrossRefGoogle Scholar
  37. 37.
    Bruce C, Chouinard RA, Tall AR: Plasma lipid transfer proteins, high-density lipoproteins, and reverse cholesterol transport. Annu Rev Nutr 1998, 18:297–330.PubMedCrossRefGoogle Scholar
  38. 38.
    Kondo I, Berg K, Drayna DT, Lawn RM: DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high density lipoprotein cholesterol and apolipoprotein levels. Clin Genet 1989, 35:49–56.PubMedCrossRefGoogle Scholar
  39. 39.
    Berg K, Kondo I, Drayna DT, Lawn RM: “Variability gene” effect of cholesteryl ester transfer protein (CETP) genes. Clin Genet 1989, 35:437–445.PubMedCrossRefGoogle Scholar
  40. 40.
    Drayna D, Lawn R: Multiple RFLP’s at the human cholesteryl ester transfer protein (CETP) locus. Nucleic Acids Res 1987, 15:4698.PubMedCrossRefGoogle Scholar
  41. 41.
    Dullaart RPF, Hoogenberg K, Riemens SC, et al.: Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid lowering diet in type I diabetes. Diabetes 1997, 46: 2082–2087.PubMedCrossRefGoogle Scholar
  42. 42.
    Ojala J-P, Helve E, Ehnholm C, et al.: Effect of apolipoprotein E polymorphism and Xbal polymorphism of apolipoprotein B on response to lovastatin treatment in familial and non-familial hypercholesterolaemia. J Intern Med 1991, 230:397–405.PubMedGoogle Scholar
  43. 43.
    O’Malley JP, Illingworth DR: The influence of apolipoprotein E phenotype on the response to lovastatin therapy in patients with heterozygous familial hypercholesterolemia. Metabolism 1990, 39:150–154.PubMedCrossRefGoogle Scholar
  44. 44.
    de Knijff P, Stalenhoef AFH, Mol MJTM, et al.: Influence of apo E polymorphism on the response to simvastatin treatment in patients with heterozygous familial hypercholesterolemia. Atherosclerosis 1990, 83:89–97.PubMedCrossRefGoogle Scholar
  45. 45.
    Sanllehy C, Casals E, Rodriguez-Villar C, et al.: Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia. Metabol Clin Exp May 1999, 47:560–565.Google Scholar
  46. 46.
    Miettinen TA, Gylling H, Strandberg T, Sarna S: Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ 1998 1999, 316:1127–1130.PubMedGoogle Scholar
  47. 47.
    Kuivenhoven JA, Jukema JW, Zwinderman AH, et al.: The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J Med 1998, 338:86–93.PubMedCrossRefGoogle Scholar
  48. 48.
    Goldstein MR: Polymorphism of the cholesteryl ester transfer protein gene. N Engl J Med 1999, 338:1624–5.CrossRefGoogle Scholar
  49. 49.
    Dullaart RP, Van Tol A: Polymorphism of the cholsteryl ester transfer protein gene. N Engl J Med 1999;338:1625–1626.Google Scholar
  50. 50.
    Vuorio AF, Ojala J-P, Sarna S, et al.: Heterozygous familial hypercholesterolaemia: the influence of the mutation type of the low-density-lipoprotein receptor gene and PvuII polymorphism of the normal allele on serum lipid levels and response to lovastatin treatment. J Intern Med 1995, 237: 43–48.PubMedCrossRefGoogle Scholar
  51. 51.
    Couture P, Brun LD, Szots F, et al.: Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous Familial Hypercholesterolemia. Arterioscler Thromb Vasc Biol 1998, 18:1007–1012.PubMedGoogle Scholar
  52. 52.
    Kajinami K, Yagi K, Higashikata T, et al.: Low-density lipoprotein receptor genotype-dependent response to cholesterol lowering by combined pravastatin and cholestyramine in Familial Hypercholesterolemia. Am J Cardiol 1998, 82: 113–117.PubMedCrossRefGoogle Scholar
  53. 53.
    Yamada M.: Influence of apolipoprotein E polymorphism on bezafibrate treatment response in dyslipidemic patients. J Atheroscler Thromb 1997, 4:40–44.PubMedGoogle Scholar

Copyright information

© Current Science Inc 1999

Authors and Affiliations

  • Jose M. Ordovas
    • 1
  • Ernst J. Schaefer
    • 1
  1. 1.Lipid Metabolism Laboratory, JM-USDA-Human Nutrition Research Center on Aging at Tufts University, Department of MedicineNew England Medical CenterBoston

Personalised recommendations