Skip to main content
SpringerLink
Log in

APOE −491 T allele may reduce the risk of atherosclerotic lesions among middle-aged women

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Genetic variability of the APOE gene confers susceptibility to coronary artery disease (CAD). Beyond variability on the coding region, polymorphisms in the regulatory region of the APOE gene have been associated with variation on plasma cholesterol levels. It has also been demonstrated a complex and multifactorial association between, APOE gene polymorphisms, gender, plasma lipids levels and risk of CAD. In the present case–control study, we examined polymorphisms −427 T/C and −491 A/T in the promoter region of APOE in relation to lipid profile and the coronary atherosclerosis, in a sample of Argentinean adults with (cases) and without (controls) atherosclerotic injuries regarding gender and age. In females below 60 years APOE −491 T allele was less prevalent in cases than in controls (OR 0.12, 95% CI 0.04–0.76). Among females cases the T allele was more frequent with increasing age (OR 0.49, 95% CI 0.27–0.90). Female up to 45 years who were carriers of the T allele showed lower levels of total (P = 0.01) and LDL cholesterol (P = 0.02) compared with non-carriers. Levels of total and LDL cholesterol increased with the age only in female carriers (P < 0.01 and P < 0.01). No differences were observed for HDL and TG levels. Allele C of polymorphism APOE −427 was associated with higher levels of triglycerides (P < 0.01). We conclude that, in middle-aged women, APOE −491 T allele contributes keeping lower levels of LDL cholesterol in the population studied, and would have a putative protective effect for the development of CAD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Rubinstein A, Colantonio L, Bardach A, Caporale J, García Martí S, Kopitowski K, Alcaraz A, Gibbons L, Augustovski F, Pichón-Rivière A (2010) Estimación de la carga de las enfermedades cardiovasculares atribuible a factores de riesgo modificables en Argentina. Rev Panam Salud Publica 27(4):237–245

    Article  PubMed  Google Scholar 

  2. Mahley RW, Rall SC (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537

    Article  PubMed  CAS  Google Scholar 

  3. DeKroon RM, Mihovilovic M, Goodger ZV, Robinette JB, Sullivan PM, Saunders AM, Strittmatter WJ (2003) APOE genotype-specific inhibition of apoptosis. J Lipid Res 44(8):1566–1573

    Article  PubMed  CAS  Google Scholar 

  4. Hui DY, Basford JE (2005) Distinct signaling mechanisms for APOE inhibition of cell migration and proliferation. Neurobiol Aging 26:317–323

    Article  PubMed  CAS  Google Scholar 

  5. Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csázár A, Utermann G (1991) The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. Am J Hum Genet 49(2):338–349

    PubMed  CAS  Google Scholar 

  6. Haviland MB, Lussier-Cacan S, Davignon J, Sing CF (1995) Impact of apolipoprotein E genotype variation on means, variances, and correlations of plasma lipid, lipoprotein, and apolipoprotein traits in octogenarians. Am J Med Genet 58(4):315–331

    Article  PubMed  CAS  Google Scholar 

  7. Hegele RA (2009) Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet 10(2):109–121

    Article  PubMed  CAS  Google Scholar 

  8. Ilveskoski E, Perola M, Lehtimäki T, Laippala P, Savolainen V, Pajarinen J, Penttilä A, Lalu KH, Männikkö A, Liesto KK, Koivula T, Karhunen PJ (1999) Age-dependent association of apolipoprotein E genotype with coronary and aortic atherosclerosis in middle-aged men: an autopsy study. Circulation 100(6):608–613

    PubMed  CAS  Google Scholar 

  9. Song Y, Stampfer MJ, Liu S (2004) Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med 141(2):137–147

    PubMed  Google Scholar 

  10. Bañares VG, Peterson G, Aguilar D, Gulayin R, Sisu E, Wyszynski DF, Pivetta OH, Tavella MJ (2005) The association between the apoe ε4 allele and atherosclerosis is age-dependent among argentine males. Hum Biol 77:247–256

    Article  PubMed  Google Scholar 

  11. Muendlein A, Saely CH, Marte T, Schmid F, Koch L, Rein P, Langer P, Aczel S, Drexel H (2008) Synergistic effects of the apolipoprotein E epsilon3/epsilon2/epsilon4, the cholesteryl ester transfer protein TaqIB, and the apolipoprotein C3–482 C & gt; T polymorphisms on their association with coronary artery disease. Atherosclerosis 199(1):179–186

    Article  PubMed  CAS  Google Scholar 

  12. Kolovou G, Damaskos D, Anagnostopoulou K, Cokkinos DV (2009) Apolipoprotein E gene polymorphism and gender. Ann Clin Lab Sci 39(2):120–133

    PubMed  CAS  Google Scholar 

  13. Corella D, Portolés O, Arriola L, Chirlaque MD, Barrricarte A, Francés F, Huerta JM, Larrañaga N, Martínez C, Martinez-Camblor P, Molina E, Navarro C, Quirós JR, Rodríguez L, Sánchez MJ, Ros E, Sala N, González CA, Moreno-Iribas C (2011) Saturated fat intake and alcohol consumption modulate the association between the APOE polymorphism and risk of future coronary heart disease: a nested case–control study in the Spanish EPIC cohort. J Nutr Biochem 22(5):487–494

    Article  PubMed  CAS  Google Scholar 

  14. Artiga MJ, Bullido MJ, Sastre I, Recuero M, García MA, Aldudo J, Vázquez J, Valdivieso F (1998) Allelic polymorphisms in the transcriptional regulatory region of apolipoprotein E gene. FEBS Lett 421(2):105–108

    Article  PubMed  CAS  Google Scholar 

  15. Laws SM, Hone E, Gandy S, Martins RN (2003) Expanding the association between the APOE gene and the risk of alzheimer’s disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription. J Neurochem 84(6):1215–1236

    Article  PubMed  CAS  Google Scholar 

  16. Bañares V, Wyszynski D, Schreier L, Tavella M (2010) APOE-219 g/T polymorphism related to serum lipid levels in atherosclerotic patients from Argentina. Invest Clin 51(1):17–26

    Google Scholar 

  17. Artieda M, Gañán A, Cenarro A, García-Otín AL, Jericó I, Civeira F, Pocoví M (2008) Association and linkage disequilibrium analyses of APOE polymorphisms in atherosclerosis. Dis Markers 24(2):65–72

    PubMed  CAS  Google Scholar 

  18. Parfenov MG, Nikolaeva TY, Sudomoina MA, Fedorova SA, Guekht AB, Gusev EI, Favorova OO (2007) Polymorphism of apolipoprotein E (APOE) and lipoprotein lipase (LPL) genes and ischaemic stroke in individuals of Yakut ethnicity. J Neurol Sci 255:42–49

    Article  PubMed  CAS  Google Scholar 

  19. Ozturk Z, Enkhmaa B, Shachter NS, Berglund L, Anuurad E (2010) Integrated role of two apoliprotein E polymorphisms on apolipoprotein B levels and coronary artery disease in a biethnic population. Metab Syndr Relat Disord 8(6):531–538

    Article  PubMed  CAS  Google Scholar 

  20. Stengård JH, Dyson G, Frikke-Schmidt R, Tybjaerg-Hansen A, Nordestgaard BG, Sing CF (2010) Context-dependent associations between variation in risk of ischemic heart disease and variation in the 5′ promoter region of the apolipoprotein E gene in Danish women. Circ Cardiovasc Genet 3(1):22–30

    Article  PubMed  Google Scholar 

  21. Lussier-Cacan S, Bolduc A, Xhignesse M, Niyonsenga T, Connelly PW, Sing CF (2000) Impact of age and body size on inter-individual variation in measures of lipid metabolism: influence of gender and apolipoprotein E genotype. Clin Genet 57(1):35–47

    Article  PubMed  CAS  Google Scholar 

  22. Ordovas JM (2007) Gender, a significant factor in the cross talk between genes, environment, and health. Gend Med 4(Suppl B):S111–S122

    Article  PubMed  Google Scholar 

  23. Hubacek JA, Lánská V, Skodová Z, Adámková V, Poledne R (2008) Sex-specific interaction between APOE and APOA5 variants and determination of plasma lipid levels. Eur J Hum Genet 16(1):135–138

    Article  PubMed  CAS  Google Scholar 

  24. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 16(3):1215

    Article  PubMed  CAS  Google Scholar 

  25. Bullido MJ, Artiga MJ, Recuero M, Sastre I, García MA, Aldudo J, Lendon C, Han SW, Morris JC, Frank A, Vázquez J, Goate A, Valdivieso F (1998) A polymorphism in the regulatory region of APOE associated with risk for alzheimer’s dementia. Nat Genet 18(1):69–71

    Article  PubMed  CAS  Google Scholar 

  26. Artiga MJ, Bullido MJ, Frank A, Sastre I, Recuero M, García MA, Lendon CL, Han SW, Morris JC, Vázquez J, Goate A, Valdivieso F (1998) Risk for alzheimer’s disease correlates with transcriptional activity of the APOE gene. Hum Mol Genet 7(12):1887–1892

    Article  PubMed  CAS  Google Scholar 

  27. Assmann G, Schriewer H, Schmitz G, Hägele EO (1983) Quantification of high-density-lipoprotein cholesterol by precipitation with phosphotungstic acid/MgCl2. Clin Chem 29(12):2026–2030

    PubMed  CAS  Google Scholar 

  28. Assmann G, Jabs HU, Kohnert U, Nolte W, Schriewer H (1984) LDL-cholesterol determination in blood serum following precipitation of LDL with polyvinylsulfate. Clin Chim Acta 140(1):77–83

    Article  PubMed  CAS  Google Scholar 

  29. Cuzick J (1985) A Wilcoxon-type test for trend. Stat Med 4:87–90

    Article  PubMed  CAS  Google Scholar 

  30. Cleves M (1999) Hardy–Weinberg equilibrium tests and allele frequency estimation. STATA Tech Bull 48:34–37

    Google Scholar 

  31. Rodríguez T, Malvezzi M, Chatenoud L, Bosetti C, Levi F, Negri E, La Vecchia C (2006) Trends in mortality from coronary heart and cerebrovascular diseases in the Americas: 1970–2000. Heart 92:453–460

    Article  PubMed  Google Scholar 

  32. Jofre-Monseny L, Minihane AM, Rimbach G (2008) Impact of APOE genotype on oxidative stress, inflammation and disease risk. Mol Nutr Food Res 52(1):131–145

    Article  PubMed  CAS  Google Scholar 

  33. Corbo RM, Scacchi R, Vilardo T, Ruggeri M (2001) Polymorphisms in the apolipoprotein E gene regulatory region in relation to coronary heart disease and their effects on plasma apolipoprotein E. Clin Chem Lab Med 39(1):2–6

    Article  PubMed  CAS  Google Scholar 

  34. Lambert JC, Brousseau T, Defosse V, Evans A, Arveiler D, Ruidavets JB, Haas B, Cambou JP, Luc G, Ducimetière P, Cambien F, Chartier-Harlin MC, Amouyel P (2000) Independent association of an APOE gene promoter polymorphism with increased risk of myocardial infarction and decreased APOE plasma concentrations-the ECTIM study. Hum Mol Genet 9(1):57–61

    Article  PubMed  CAS  Google Scholar 

  35. Alvarez-Arcaya A, Combarros O, Llorca J, Sánchez-Guerra M, Berciano J, Fernández-Luna JL (2001) The -491 TT apolipoprotein E promoter polymorphism is associated with reduced risk for sporadic alzheimer’s disease. Neurosci Lett 304(3):204–208

    Article  PubMed  CAS  Google Scholar 

  36. Klinge CM (2001) Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 29:2905–2919

    Article  PubMed  CAS  Google Scholar 

  37. Lambert JC, Coyle N, Lendon C (2004) The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for alzheimer’s disease. J Med Genet 41:104–112

    Article  PubMed  CAS  Google Scholar 

  38. Struble RG, Cady C, Nathan BP, McAsey M (2008) Apolipoprotein E may be a critical factor in hormone therapy neuroprotection. Front Biosci 13:5387–5405

    Article  PubMed  CAS  Google Scholar 

  39. Colditz GA, Willet WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH (1987) Menopause and the risk of coronary heart disease in women. N Engl J Med 316:1105–1110

    Article  PubMed  CAS  Google Scholar 

  40. Stevenson JC, Crook D, Godsland IF (1993) Effects of age and menopause on lipid metabolism in health women. Atherosclerosis 98:83–90

    Article  PubMed  CAS  Google Scholar 

  41. Lobo RA (1991) Effects of hormone replacement on lipids and lipoproteins in postmenopausal women. J Clin Endocrinol Metab 73:925–930

    Article  PubMed  CAS  Google Scholar 

  42. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM (1991) Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med 325:1196–1204

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by: A.N.L.I.S (Administración Nacional de Laboratorios e Institutos de Salud) “Dr. C Malbrán”; and CONICET (Comisión Nacional de Investigaciones Científicas y Tecnológicas) Argentina.

Author information

Authors and Affiliations

  1. Instituto Nacional de Genética Médica, Administración Nacional de Laboratorios e Institutos de Salud “Dr. Carlos Malbrán”, Buenos Aires, Argentina

    Virginia G. Bañares

  2. PROPIA (Programa de Prevención del Infarto en Argentina), CIC (Comisión de Investigaciones Científicas de la Provincia de Buenos Aires), Universidad Nacional de La Plata, La Plata, Argentina

    Virginia G. Bañares, Ariel Bardach, Graciela Peterson & Marcelo J. Tavella

  3. Instituto de Investigaciones Bioquímicas de La Plata, La Plata, Argentina

    Marcelo J. Tavella

  4. Laboratorio de Lípidos y Lipoproteínas, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Laura E. Schreier

  5. Santa Rosa 2801 UF6, 1644, Victoria (San Fernando) Buenos Aires, Argentina

    Virginia G. Bañares

Authors
  1. Virginia G. Bañares
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ariel Bardach
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graciela Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcelo J. Tavella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laura E. Schreier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Virginia G. Bañares.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bañares, V.G., Bardach, A., Peterson, G. et al. APOE −491 T allele may reduce the risk of atherosclerotic lesions among middle-aged women. Mol Cell Biochem 362, 123–131 (2012). https://doi.org/10.1007/s11010-011-1134-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-1134-5

Keywords

Search

Navigation