Current Cardiology Reports

, Volume 4, Issue 6, pp 508–513 | Cite as

Genetics, the environment, and lipid abnormalities

  • Jose M. Ordovas
  • Haiqing Shen


Plasma lipid levels have been identified as major risk factors for cardiovascular disease. Multiple behavioral and environmental factors are known to modulate their concentrations in the general population; however, there is dramatic individual variability in the association between risk factors and disease, as well as in the individual response to therapeutic intervention. These differences may be due to the interaction between genetic and nongenetic factors that are ultimately responsible for the individual disease risk and response to intervention. Great strides have been made to characterize the genes involved in the homeostasis of plasma lipoprotein levels and to identify polymorphisms that could contribute to an earlier and more precise individual risk assessment. Especially relevant has been the recent interest and progress on examining the interaction between a number of candidate genes and nongenetic factors, namely smoking, alcohol drinking, physical activity, and sex. The APOE locus continues to be the most thoroughly studied gene in this regard; however, other genes (ie, LPL, APOC3, ADH3) are showing promising results.


Plasma Lipid APOE Genotype Arterioscler Thromb Vasc Biol APOE Gene Plasma Lipid Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    McCrae T. Osler: Principles and Practice of Medicine. London: Appleton; 1912:836.Google Scholar
  2. 2.
    Ordovas JM: Gene-diet interaction and plasma lipid responses to dietary intervention. Biochem Soc Trans 2002, 30:68–73.PubMedCrossRefGoogle Scholar
  3. 3.
    Ordovas JM, Shen H: Pharmacogenetics of lipid-lowering Therapies. Curr Atheroscler Rep 2002, 4:183–192.PubMedGoogle Scholar
  4. 4.
    Ordovas JM, Mooser V: The APOE locus and the pharmacogenetics of lipid response. Curr Opin Lipidol 2002, 13:113–117.PubMedCrossRefGoogle Scholar
  5. 5.
    Talmud PJ, Humphries SE: Gene-environment interaction in lipid metabolism and effect on coronary heart disease risk. Curr Opin Lipidol 2002, 13:149–154.PubMedCrossRefGoogle Scholar
  6. 6.
    Weinberg RB: Apolipoprotein A-IV polymorphisms and diet-gene interactions. Curr Opin Lipidol 2002, 13:125–134.PubMedCrossRefGoogle Scholar
  7. 7.
    Krauss RM: Dietary and genetic effects on low-density lipoprotein heterogeneity. Ann Rev Nutr 2001, 21:283–295.CrossRefGoogle Scholar
  8. 8.
    Humphries SE, Talmud PJ, Hawe E, et al.: Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study. Lancet 2001, 358:115–119. This research highlights the interaction between APOE, smoking, and CHD for men. The findings indicate that carriers of the E4 allele who smoke are at much higher risk than those who don’t smoke. Quite intriguing, but not surprising, was the fact that these effects were observed independently of plasma lipid levels.PubMedCrossRefGoogle Scholar
  9. 9.
    Malin R, Loimaala A, Nenonen A, et al.: Relationship between high-density lipoprotein paraoxonase gene M/L55 polymorphism and carotid atherosclerosis differs in smoking and nonsmoking men. Metabolism 2001, 50:1095–1101.PubMedCrossRefGoogle Scholar
  10. 10.
    Perez-Martinez P, Gomez P, Paz E, et al.: Interaction between smoking and the Sstl polymorphism of the apo C-III gene determines plasma lipid response to diet. Nutr Metab Cardiovasc Dis 2001, 11:237–243.PubMedGoogle Scholar
  11. 11.
    Corella D, Tucker K, Lahoz C, et al.: Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: the Framingham Offspring Study. Am J Clin Nutr 2001, 73:736–745. This research reports an interesting observation suggesting that alcohol may be one of the environmental factors that triggers the associations between plasma lipids and APOE alleles. The data from the Framingham Study show that in men who don’t drink, there is no effect of the APOE alleles on LDL cholesterol concentrations. Such observation was not seen in women.PubMedGoogle Scholar
  12. 12.
    Djousse L, Myers RH, Province MA, et al.: Influence of apolipo-protein E, smoking, and alcohol intake on carotid atherosclerosis: National Heart, Lung, and Blood Institute Family Heart Study. Stroke 2002, 33:1357–1361. This paper reinforces the findings observed by Humphries et al. [8 ].PubMedCrossRefGoogle Scholar
  13. 13.
    Higgins M, Province M, Heiss G, et al.: NHLBI Family Heart Study: objectives and design. Am J Epidemiol 1996, 143:1219–1228.PubMedGoogle Scholar
  14. 14.
    Lussier-Cacan S, Bolduc A, Xhignesse M, et al.: Impact of alcohol intake on measures of lipid metabolism depends on context defined by gender, body mass index, cigarette smoking, and apolipoprotein E genotype. Arterioscler Thromb Vasc Biol 2002, 22:824–831. A very comprehensive analyses of the context dependent associations between the APOE gene and plasma lipid levels, with emphasis on BMI.PubMedCrossRefGoogle Scholar
  15. 15.
    McGladdery SH, Frohlich JJ: Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy. J Lipid Res 2001, 42:1905–1912.PubMedGoogle Scholar
  16. 16.
    Hubinette A, Cnattingius S, et al.: Birthweight, early environment, and genetics: a study of twins discordant for acute myocardial infarction. Lancet 2001, 357:1997–2001.PubMedCrossRefGoogle Scholar
  17. 17.
    Corella D, Guillen M, Saiz C, et al.: Environmental factors modulate the effect of the APOE genetic polymorphism on plasma lipid concentrations: ecogenetic studies in a Mediter-ranean Spanish population. Metabolism 2001, 50:936–944.PubMedCrossRefGoogle Scholar
  18. 18.
    Bernstein MS, Costanza MC, James RW, et al.: Physical activity may modulate effects of ApoE genotype on lipid profile. Arterioscler Thromb Vasc Biol 2002, 22:133–140.PubMedCrossRefGoogle Scholar
  19. 19.
    Hagberg JM, Ferrell RE, Katzel LI, et al.: Apolipoprotein E genotype and exercise training-induced increases in plasma high-density lipoprotein (HDL)- and HDL2-cholesterol levels in overweight men. Metabolism 1999, 48:943–945.PubMedCrossRefGoogle Scholar
  20. 20.
    Plat J, Mensink RP: Effects of plant stanol esters on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase mRNA expression in mononuclear blood cells of healthy men and women. FASEB J 2002, 16:258–260.PubMedCrossRefGoogle Scholar
  21. 21.
    Tai ES, Demissie S, Cupples LA, et al.: Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 2002, 22:805–810. This research demonstrates the highly relevant role of the PPARα locus in determining the variability of LDL cholesterol concentrations in the general population. Moreover, it unfolds some very interesting gene-gene interactions that may explain, in addition to environmental factors, the impact of the this locus on LDL cholesterol levels.PubMedCrossRefGoogle Scholar
  22. 22.
    Corella D, Guillen M, Saiz C, et al.: Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population. Interaction with tobacco smoking and the apoe locus. J Lipid Res 2002, 43:416–427.PubMedGoogle Scholar
  23. 23.
    Viitanen L, Pihlajamaki J, Miettinen R, et al.: Apolipoprotein E gene promoter (-219G/T) polymorphism is associated with premature coronary heart disease. J Mol Med 2001, 79:732–737.PubMedCrossRefGoogle Scholar
  24. 24.
    Corbo RM, Scacchi R, Vilardo T, Ruggeri M: Polymorphisms in the apolipoprotein E gene regulatory region in relation to coronary heart disease and their effect on plasma apolipoprotein E. Clin Chem Lab Med 2001, 39:2–6.PubMedCrossRefGoogle Scholar
  25. 25.
    McLaughlin DP, Sharma A, McGinley A, Samra GS: The advantages of haplotype analysis of the promoter region of the human apolipoprotein E gene. Anal Biochem 2001, 299:183–187.PubMedCrossRefGoogle Scholar
  26. 26.
    Ukkola O, Tremblay A, Bouchard C: Lipoprotein lipase polymorphisms and responses to long-term overfeeding. J Intern Med 2002, 251:429–436.PubMedCrossRefGoogle Scholar
  27. 27.
    Garenc C, Perusse L, Bergeron J, et al.: Evidence of LPL gene-exercise interaction for body fat and LPL activity: the HERITAGE Family Study. J Appl Physiol 2001, 91:1334–1340.PubMedGoogle Scholar
  28. 28.
    Senti M, Elosua R, Tomas M, et al.: Physical activity modulates the combined effect of a common variant of the lipoprotein lipase gene and smoking on serum triglyceride levels and high-density lipoprotein cholesterol in men. Hum Genet 2001, 109:385–392.PubMedCrossRefGoogle Scholar
  29. 29.
    Hines LM, Stampfer MJ, Ma J, et al.: Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001, 344:549–555. This research supports the concept for APOE that the benefit moderate alcohol consumption on CVD risk may be gene-dependent.PubMedCrossRefGoogle Scholar
  30. 30.
    Belanger CF, Hennekens CH, Rosner B, Speizer FE: The Nurse’s Health Study. Am J Nurs 1978, 78:1039–1040.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2002

Authors and Affiliations

  • Jose M. Ordovas
    • 1
  • Haiqing Shen
    • 1
  1. 1.Nutrition and Genomics LaboratoryJM-USDA-Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA

Personalised recommendations