Advertisement

Hormones

, Volume 14, Issue 3, pp 376–382 | Cite as

Study of common variants of the apolipoprotein E and lipoprotein lipase genes in patients with coronary heart disease and variable body mass index

  • Genovefa D. Kolovou
  • Vana Kolovou
  • Demosthenes B. Panagiotakos
  • Ioannis Vasiliadis
  • Vassiliki Giannakopoulou
  • Peggy M. Kostakou
  • Vassiliki Vartela
  • Sophie Mavrogeni
Research paper

Abstract

OBJECTIVE

In the present study, we evaluated the influence of lipoprotein lipase (LPL) and apolipoprotein (apo) E polymorphisms on lipid concentrations of 178 Greek men of similar age with coronary heart disease (CHD), but varying body mass index (BMI).

DESIGN

Patients were divided according to their BMI (in kg/m2) into three groups: lean (BMI=20–24.9), overweight (BMI=25–29.9), and obese (BMI ≥30). Polymorphisms of LPL (HindIII, S447X) and apo E (ε2, ε3, ε4), and lipid parameters were studied.

RESULTS

There was a negative correlation between BMI and high-density lipoprotein cholesterol (HDL-C) concentration (r=−0.272, p<0.001), as has already been described. Lean homozygotes for the HindIII(+) allele had higher HDL-C levels compared to lean homozygotes for the HindIII(−) allele (p=0.012). No correlation was found between S447X or apo E polymorphisms and BMI or plasma lipids in any group. Overweight men with the ε3/ε3 and SS genotypes had higher triglycerides concentration compared with overweight men with ε3/ε3 and SX (p=0.002).

CONCLUSIONS

The HindIII polymorphism alone may influence HDL-C concentration in lean men, in contrast to S447X alone, which has no influence on any lipid parameters. However, the S447X and apo E polymorphisms may have a synergetic effect and alter plasma triglyceride concentration in overweight men.

Key words

Apolipoprotein E Body mass index Coronary heart disease Lipids Lipoprotein lipase Polymorphism 

References

  1. 1.
    Parekh S, Anania FA, 2007 Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease. Gastroenterology 132: 2191–2207.CrossRefGoogle Scholar
  2. 2.
    Qureshi K, Abrams GA, 2007 Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol: 13: 3540–3553.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chan DC, Barrett HP, Watts GF, 2004 Dyslipidemia in visceral obesity: mechanisms, implications, and therapy. Am J Cardiovasc Drugs 4: 227–246.CrossRefGoogle Scholar
  4. 4.
    Shimo-Nakanishi Y, Urabe T, Hattori N, et al, 2001 Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. Stroke 32: 1481–1486.CrossRefGoogle Scholar
  5. 5.
    Song Y, Stampfer MJ, Liu S, 2004 Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med 141: 137–147.CrossRefGoogle Scholar
  6. 6.
    Kolovou G, Daskalova D, Mikhailidis DP, 2003 Apolipoprotein E polymorphism and atherosclerosis. Angiology 54: 59–71.CrossRefGoogle Scholar
  7. 7.
    Pykälistö OJ, Smith PH, Brunzell JD, 1975 Determinants of human adipose tissue lipoprotein lipase: effect of diabetes and obesity on basal- and diet-induced activity. J Clin Invest 56: 1108–1117.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Taylor KG, Holdsworth G, Galton DJ, 1977 Clofibrate increases lipoprotein-lipase activity in adipose tissue of hypertriglyceridaemic patients. Lancet 8048: 1106–1107.CrossRefGoogle Scholar
  9. 9.
    Eckel RH, 1989 Lipoprotein lipase: a multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 320: 1060–1067.CrossRefGoogle Scholar
  10. 10.
    Beisiegel U, Weber W, Bengtsson-Olivecrona G, 1991 Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. Proc Natl Acad Sci USA 88: 8342–8346.CrossRefGoogle Scholar
  11. 11.
    Mulder M, Lombardi P, Jansen H, van Berkel TJ, Frants RR, Havekes LM, 1993 Low density lipoprotein receptor internalizes low density and very low density lipoproteins that are bound to heparan sulfate proteoglycans via lipoprotein lipase. J Biol Chem 268: 9369–9375.PubMedGoogle Scholar
  12. 12.
    Salinelli S, Lo JY, Mims MP, Zsigmond E, Smith LC, Chan L, 1996 Structure-function relationship of lipoprotein lipase-mediated enhancement of very low density lipoprotein binding and catabolism by the low density lipoprotein receptor: functional importance of a properly folded surface loop covering the catalytic center. J Biol Chem 271: 21906–21913.CrossRefGoogle Scholar
  13. 13.
    Jemaa R, Fumeron F, Poirier O, et al, 1995 Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude Cas Témoin sur l’Infarctus du Myocarde. J Lipid Res 36: 2141–2146.PubMedGoogle Scholar
  14. 14.
    Groenemeijer BE, Hallman MD, Reymer PW, et al, 1997 Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group. Circulation 95: 2628–2635.CrossRefGoogle Scholar
  15. 15.
    Anagnostopoulou KK, Kolovou GD, Kostakou PM, et al, 2009 Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia. Lipids Health Dis 26: 24.CrossRefGoogle Scholar
  16. 16.
    Henderson HE, Kastelein JJ, Zwinderman AH, et al, 1999 Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. J Lipid Res 40: 735–743.PubMedGoogle Scholar
  17. 17.
    Kuivenhoven JA, Groenemeyer BE, Boer JM, et al, 1997 Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males. Arterioscler Thromb Vasc Biol 17: 595–599.CrossRefGoogle Scholar
  18. 18.
    Gigek Cde O, Chen ES, Cendoroglo MS, et al, 2007 Association of lipase lipoprotein polymorphisms with myocardial infarction and lipid levels. Clin Chem Lab Med 45: 599–604.PubMedGoogle Scholar
  19. 19.
    Wung SF, Kulkarni MV, Pullinger CR, Malloy MJ, Kane JP, Aouizerat BE, 2006 The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion. Lipids Health Dis 5: 19.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Almeida KA, Strunz CM, Maranhao RC, Mansur AP, 2007 The S447X polymorphism of lipoprotein lipase: effect on the incidence of premature coronary disease and on plasma lipids. Arq Bras Cardiol 88: 297–303.CrossRefGoogle Scholar
  21. 21.
    Peacock RE, Hamsten A, Nilsson-Ehle P, 1992 Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden. Atherosclerosis 97: 171–185.CrossRefGoogle Scholar
  22. 22.
    Georges JL, Regis-Bailly A, Salah D, 1996 Family study of lipoprotein lipase gene polymorphisms and plasma triglyceride levels. Genet Epidemiol 13: 179–192.CrossRefGoogle Scholar
  23. 23.
    Razzaghi H, Aston CE, Hamman RF, 2000 Genetic screening of the lipoprotein lipase gene for mutations associated with high triglyceride/low HDL-cholesterol levels. Hum Genet 107: 257–267.CrossRefGoogle Scholar
  24. 24.
    Malygina NA, Melent’ev AS, Kostomarova IV, 2001 Connection of HindIII-polymorphism in the lipoprotein lipase gene with myocardial infarct and life span in elderly ischemic heart disease patients. Mol Biol (Mosk) 35: 787–791.CrossRefGoogle Scholar
  25. 25.
    Mahley RW, 1988 Apolipoprotein E, cholesterol transport protein with expanding role in cell biology. Science 240: 622–630.CrossRefGoogle Scholar
  26. 26.
    Mahley RW, Rall SC Jr, 2000 Apolipoprotein E, far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1: 507–537.CrossRefGoogle Scholar
  27. 27.
    Kolovou G, Damaskos D, Anagnostopoulou K, Cokkinos DV, 2009 Apolipoprotein E gene polymorphism and gender. Ann Clin Lab Sci 39: 120–133.PubMedGoogle Scholar
  28. 28.
    Kolovou GD, Anagnostopoulou KK, Kostakou P, et al, 2009 Apolipoprotein E gene polymorphism and obesity status in middle-aged men with coronary heart disease. In Vivo 23: 33–39.PubMedGoogle Scholar
  29. 29.
    Kolovou GD, Anagnostopoulou KK, Cokkinos DV, 2009 Apolipoprotein E gene polymorphism and myocardial infarction. Int J Cardiol 133: 264–265.CrossRefGoogle Scholar
  30. 30.
    Muros M, Rodriguez-Ferrer C, 1996 Apolipoprotein E polymorphism influence on lipids, apolipoproteins and Lp(a) in a Spanish population underexpressing apo E4. Atherosclerosis 121: 13–21.CrossRefGoogle Scholar
  31. 31.
    Gómez-Coronado D, Alvarez JJ, Entrala A, Olmos JM, Herrera E, Lasunción MA, 1999 Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins. Atherosclerosis 147: 167–176.CrossRefGoogle Scholar
  32. 32.
    Humphries SE, Nicaud V, Margalef J, Tiret L, Talmud PJ, 1998 Lipoprotein lipase gene variation is associated with a paternal history of premature coronary artery disease and fasting and postprandial plasma triglycerides: the European Atherosclerosis Research Study (EARS). Arterioscler Thromb Vasc Biol 18: 526–534.CrossRefGoogle Scholar
  33. 33.
    Hixson JE, Vernier DT, 1990 Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with Hhal. J Lipid Res 31: 545–548.PubMedGoogle Scholar
  34. 34.
    Kolovou G, Yiannakouris N, Hatzivassiliou M, et al, 2002 Association of apolipoprotein E polymorphism with myocardial infarction in Greek patients with coronary artery disease. Curr Med Res Opin 18: 118–124.CrossRefGoogle Scholar
  35. 35.
    Xin X, Srinivasan SR, Chen W, Boerwinkle E, Berenson GS, 2003 Interaction effect of Serine447Stop variant of the lipoprotein lipase gene and C-514T variant of the hepatic lipase gene on serum triglyceride levels in young adults: the Bogalusa Heart Study. Metabolism 52: 1337–1342.CrossRefGoogle Scholar
  36. 36.
    Barg E, 2011 Polymorphisms of lipoprotein lipase gene and their participation in metabolic processes. Pediatr Endocrinol Diabetes Metab 17: 107–112.PubMedGoogle Scholar
  37. 37.
    Agirbasli M, Sumerkan MC, Eren F, Agirbasli D, 2011 The S447X variant of lipoprotein lipase gene is inversely associated with severity of coronary artery disease. Heart Vessels 26: 457–463.CrossRefGoogle Scholar
  38. 38.
    Baik I, Lee S, Kim SH, Shin C, 2013 Lipoprotein Lipase Gene Polymorphism Interacts with Consumption of Alcohol and Unsaturated Fat to Modulate Serum HDL-Cholesterol Concentrations. J Nutr 143: 1618–1625.CrossRefGoogle Scholar
  39. 39.
    Aydogan HY, Isbir S, Kurnaz O, Gormus U, Isbir T, 2009 Associations of lipoprotein lipase S447X and apolipoprotein E genotypes with low-density lipoprotein subfractions in Turkish patients with coronary artery disease. In Vivo 23: 155–161.PubMedGoogle Scholar
  40. 40.
    Abd-El-Aziz TA, Mohamed RH, El-Shal AS, 2013 Synergistic effect between lipoprotein lipase and apolipoprotein C3 genes in determining the severity of coronary artery disease. J Cardiovasc Transi Res 6: 430–435.CrossRefGoogle Scholar
  41. 41.
    Al-Jafari AA, Daoud MS, Mobeirek AF, Al Anazi MS, 2012 DNA polymorphisms of the lipoprotein lipase gene and their association with coronary artery disease in the Saudi population. Int J Mol Sci 13: 7559–7574.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Munshi A, Babu MS, Kaul S, Rajeshwar K, Balakrishna N, Jyothy A, 2012 Association of LPL gene variant and LDL, HDL, VLDL cholesterol and triglyceride levels with ischemic stroke and its subtypes. J Neurol Sci 318: 51–54.CrossRefGoogle Scholar
  43. 43.
    Muñoz-Barrios S, Guzmán-Guzmán IP, Muñoz-Valle JF, Salgado-Bernabé AB, Salgado-Goytia L, Parra-Rojas I, 2012 Association of the HindIII and S447X polymorphisms in LPL gene with hypertension and type 2 diabetes in Mexican families. Dis Markers 33: 313–320.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Rebhi L, Kchok K, Omezzine A, et al, 2012 Six lipoprotein lipase gene polymorphisms, lipid profile and coronary stenosis in a Tunisian population. Mol Biol Rep 39: 9893–9901.CrossRefGoogle Scholar
  45. 45.
    Wang XL, McCredie RM, Wilcken DEL, 1996 Common DNA Polymorphisms at the Lipoprotein Lipase Gene: Association with Severity of Coronary Artery Disease and Diabetes Circulation 93: 1339–1345.CrossRefGoogle Scholar
  46. 46.
    Ma YQ, Thomas GN, Ng MC, Critchley JA, Chan JC, Tomlinson B, 2003 The lipoprotein lipase gene HindIII polymorphism is associated with lipid levels in early-onset type 2 diabetic patients. Metabolism 52: 338–343.CrossRefGoogle Scholar
  47. 47.
    Mitchell RJ, Earl L, Bray P, Fripp YJ, Williams J, 1994 DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides. Hum Biol 66: 383–397.PubMedGoogle Scholar
  48. 48.
    Peacock RE, Hamsten A, Nilsson-Ehle P, Humphries SE, 1992 Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden. Atherosclerosis 97: 171–185.CrossRefGoogle Scholar
  49. 49.
    Heinzmann C, Kirchgessner T, Kwiterovich PO, et al, 1991 DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible associations with high-density lipoprotein levels. Hum Genet 86: 578–584.Google Scholar
  50. 50.
    Vohl MC, Lamarche B, Moorjani S, et al, 1995 The lipoprotein lipase HindIII polymorphism modulates plasma triglyceride levels in visceral obesity. Arterioscler Thromb Vasc Biol 15: 714–720.CrossRefGoogle Scholar
  51. 51.
    Jemaa R, Tuzet S, Portos C, Betoulle D, Apfelbaum M, Fumeron F, 1995 Lipoprotein lipase gene polymorphisms: associations with hypertriglyceridemia and body mass index in obese people. Int J Obes Relat Metab Disord 19: 270–274.PubMedGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2015

Authors and Affiliations

  • Genovefa D. Kolovou
    • 1
  • Vana Kolovou
    • 1
    • 2
  • Demosthenes B. Panagiotakos
    • 3
  • Ioannis Vasiliadis
    • 1
    • 4
  • Vassiliki Giannakopoulou
    • 5
  • Peggy M. Kostakou
    • 5
  • Vassiliki Vartela
    • 1
  • Sophie Mavrogeni
    • 1
  1. 1.Cardiology DepartmentOnassis Cardiac Surgery CenterAthensGreece
  2. 2.Molecular Immunology LaboratoryOnassis Cardiac Surgery CenterAthensGreece
  3. 3.Harokopio UniversityAthensGreece
  4. 4.Royal Free Hospital-University College of London (UCL)LondonUK
  5. 5.Cardiology DepartmentThriassio General HospitalAthensGreece

Personalised recommendations