Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

See all formats and pricing
More options …
Volume 43, Issue 9


APOE genotypes and dyslipidemias in a sample of the Portuguese population

Maria Odete Rodrigues
  • Centro de Biopatologia, Centro de Epidemiologia e Bioestatística, Instituto Nacional de Saúde, Lisboa, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Aidil Fonseca
  • Centro de Biopatologia, Centro de Epidemiologia e Bioestatística, Instituto Nacional de Saúde, Lisboa, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Carlos Matias Dias
  • Observatório Nacional de Saúde, Centro de Epidemiologia e Bioestatística, Instituto Nacional de Saúde, Lisboa, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Isabel Albergaria
  • Centro de Biopatologia, Centro de Epidemiologia e Bioestatística, Instituto Nacional de Saúde, Lisboa, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gisela Martins
  • Centro de Biopatologia, Centro de Epidemiologia e Bioestatística, Instituto Nacional de Saúde, Lisboa, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maria Liseta Alpendre
  • Centro de Biopatologia, Centro de Epidemiologia e Bioestatística, Instituto Nacional de Saúde, Lisboa, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maria do Carmo Martins
  • Centro de Biopatologia, Centro de Epidemiologia e Bioestatística, Instituto Nacional de Saúde, Lisboa, Portugal
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2005-09-22 | DOI: https://doi.org/10.1515/CCLM.2005.155


The objective of this work was to study the distribution of apolipoprotein E ( APOE) genotypes in a sample of the Portuguese population, and its association with the dyslipidemias observed. Study participants were healthy users of local Public Health Laboratories in six regions of mainland Portugal (Porto, Vila Real, Viseu, Lisboa, Portalegre and Faro). A total of 779 men and 1153 women aged 15–74years agreed to participate. Fasting lipid levels and APOE genotypes were determined centrally at the National Institute of Health in Lisboa. The frequency distribution of APOE alleles was: ε2=5.3%, ε3=84.9% and ε4=9.8%. Dyslipidemias were present in 66.6% of men and 60.7% of women. Comparison of APOE genotypes and relative allele frequencies showed that in dyslipidemic compared to normolipidemic subjects, the ε4 allele was more frequent in both sexes, although in a more pronounced way in men than in women due to higher frequencies of ε3/ ε4 and ε4/ ε4 genotypes. The known association of the ε4 allele with high cholesterol levels, the association of the ε2 allele with low cholesterol levels, and the association of the ε2 allele with high levels of triglycerides and low levels of high-density lipoprotein-cholesterol were confirmed in this study.

Keywords: APOE genotypes; cardiovascular diseases; dyslipidemias; Portuguese regions


  • 1.

    Siest G, Pillot T, Regis-Bailly A, Leininger-Muller B, Steinmetz J, Galteau MM, et al. Apolipoprotein E: an important gene and protein to follow in laboratory medicine. Clin Chem 1995; 41: 1068–86. Google Scholar

  • 2.

    Mahley RW, Weisgraber KH, Thomas L, Rall SC Jr. Genetic defects in lipoprotein metabolism. Elevation of atherogenic lipoproteins caused by impaired catabolism. J Am Med Assoc 1991; 265: 78–83. Google Scholar

  • 3.

    Mahley RW. Apoliporotein E. Cholesterol transport protein with expanding role in cell biology. Science 1988; 240: 622–30. Google Scholar

  • 4.

    Gregg RE, Brewer HB Jr. The role of apolipoprotein E and lipoprotein receptors in modulating the in vivo metabolism of apoliprotein B-containing lipoproteins in humans. Clin Chem 1988; 34: B28–B32. Google Scholar

  • 5.

    Kwijft P, Maagdenberg AM, Frants RR, Havekes LM. Genetic heterogeneity of apolipoprotein E and its influence on plasma lipid and lipoprotein levels. Hum Mutat 1994; 4: 178–94. CrossrefGoogle Scholar

  • 6.

    Dallongeville J, Lussier-Cacan S, Davignon J. Modulation of plasma triglycerides levels by apoE phenotype: a meta-analysis. J Lipid Res 1992; 33: 447–54. Google Scholar

  • 7.

    Wilson PW, Myers RH, Larson MG, Ordovas JM, Wolf PA, Schaefer EJ. Apolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study. J Am Med Assoc 1994; 272: h1666–71. Google Scholar

  • 8.

    Davignon J, Gregg RE, Sing CF. Apolipoprotein E and atherosclerosis. Atherosclerosis 1988; 8: 1–21. Google Scholar

  • 9.

    Franco A, Martinho MC, Martins MC. Estudo prospectivo de lípidos sanguíneos em amostras da população Portuguesa. Arquivos do INSA 1980; IV: 263–92. Google Scholar

  • 10.

    Franco A, Martinho MC, Martins MC. Os lípidos sanguíneos na doença cardíaca isquémica. Arquivos do INSA 1981; VI: 355–79. Google Scholar

  • 11.

    Martins MC, Rodrigues MO, Gomes MA, Fonseca A, Faleiro LL. Lípidos em crianças e jovens. Um problema de Saúde Pública. Acta Med Port 1995; 8: 477–83. Google Scholar

  • 12.

    Direcção Geral da Saúde. DSIA, Divisão de Epidemiologia. Risco de morrer em Portugal. Lisboa: Direcção Geral da Saúde, 1999:29–52. Google Scholar

  • 13.

    Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215. CrossrefGoogle Scholar

  • 14.

    Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990; 31: 545–8. Google Scholar

  • 15.

    Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J Am Med Assoc 2001;285:2486–97. Google Scholar

  • 16.

    Schiele F, De Bacquer D, Vincent-Viry M, Beisiegel U, Ehnholm C, Evans A, et al. Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project. Atherosclerosis 2000; 152: 475–88. Google Scholar

  • 17.

    Mahley RW, Rall SC Jr. Type III hyperlipoproteinemia (dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal lipoprotein metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 1995:1953–80. Google Scholar

  • 18.

    Lahlali-Kacemi N, Bamon Y, Guedira A, Hassani M, Visvikis S, Siest G, et al. Polymorphisme de l'apolipoprotéine E dans une population Morocaine: fréquence allélique et relation avec les paramètres lipidiques plasmatiques. Ann Biol Clin 2002; 60: 73–8. Google Scholar

  • 19.

    Lenzen HJ, Assmann G, Buchwaisky R, Schulte H. Association of apolipoprotein E polymorphism, low-density lipoprotein cholesterol, and coronary artery disease. Clin Chem 1986; 32: 778–81. Google Scholar

  • 20.

    Ministério da Saúde. Direcção Geral de Saúde. Ganhos de Saúde em Portugal: Relatório do Director Geral e Alto-Comissário da Saúde. Lisboa: Direcção Geral da Saúde, 2002:113–6. Google Scholar

  • 21.

    Galton DJ. Genetic determinants of atherosclerosis related dyslipidemias and their clinical implications. Clin Chim Acta 1997; 257: 181–97. Google Scholar

  • 22.

    Brown BG, Zhao XQ, Sacco DE, Albers JJ. Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993; 87: 1781–91. CrossrefGoogle Scholar

  • 23.

    Lindenstrom E, Boysen G, Nyboe J. Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study. Br Med J 1994; 309: 11–5. Google Scholar

  • 24.

    Pedersen TR, Kjekshus J, Berg K, Haghfelt T, Faergeman O, Faergeman G, et al. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9. Google Scholar

  • 25.

    Assmann G, Gotto AM Jr, Paoletti R. The hypertriglyceridemias: risk and management. Am J Cardiol 1991; 68: 1A–4A. CrossrefGoogle Scholar

  • 26.

    Schachter M. The pathogenesis of atherosclerosis. Int J Cardiol 1997; 62: 3–7. CrossrefWeb of ScienceGoogle Scholar

  • 27.

    Libby P, Sukhova G, Lee RT, Liao JK. Molecular biology of atherosclerosis. Int J Cardiol 19971; 62(Suppl 2): S23–9. Google Scholar

  • 28.

    Hofker M. Lipoxygenases at the heart of atherosclerosis susceptibility. Eur J Hum Genet 2004; 12: 601–2. CrossrefGoogle Scholar

  • 29.

    Grundy SM. Inflammation, hypertension, and the metabolic syndrome [editorial]. J Am Med Assoc 2003; 290: 3000–2. Google Scholar

  • 30.

    Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115–26. Google Scholar

  • 31.

    Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801–8. Google Scholar

  • 32.

    Shepherd J, Krauss RM. Pathophysiology of triglyceride-rich particles. A. Metabolism of triglyceride-rich particles. Am J Cardiol 1991; 68: 5A–7A. Google Scholar

  • 33.

    Poulter NR. High-density lipoprotein and coronary artery disease: the fibrate renaissance – introduction. Am J Cardiol 2001; 88: 1N–2N. CrossrefGoogle Scholar

  • 34.

    Libby P. Managing the risk of atherosclerosis: the role of high-density lipoprotein. Am J Cardiol 2001; 88: 3N–8N. CrossrefGoogle Scholar

  • 35.

    Ministério da Saúde, Direcção Geral da Saúde. Programa Nacional de Prevenção e Controlo das DCV – Circular Normativa da Direcção Geral de Saúde 05/09/03. Lisboa: Direcção Geral da Saúde, 2003. Google Scholar

  • 36.

    Silva PM, Silva JM, Gil VM. Prevenção cardiovascular: recomendações para a abordagem do risco vascular associado às dislipidémias. Rev Port Cardiol 2002; 21: 1201–9. Google Scholar

  • 37.

    Sousa JC, Pinto DS. Valores laboratoriais do estudo lipídico e risco vascular. Rev Fac Med Lisboa Ser III 2003; 8: 75–81. Google Scholar

  • 38.

    Alaupovic P, McConathy WJ, Fesmire J, Tavella M, Bard JM. Profiles of apolipoproteins and apolipoprotein B-containing lipoprotein particles in dyslipoproteinemias. Clin Chem 1988; 34: B13–B27. Google Scholar

  • 39.

    Schaefer EJ, McNamara JR, Genest J, Ordovas JM. Genetics and abnormalities in metabolism of lipoproteins. Clin Chem 1988; 34: B9–B12. Google Scholar

  • 40.

    Patsch W, Franz S, Shonfeld G. Role of insulin in lipoprotein secretion by cultured rat hepatocytes. J Clin Invest 1983; 71: 1161–74. Google Scholar

  • 41.

    Amorim Cruz JA. A evolução dos consumos alimentares em Portugal nas últimas 4 décadas. Rev Port Nutr 1999; 9: 5–15. Google Scholar

  • 42.

    Amorim Cruz JA. Alimentação e Saúde em Portugal: estudo ecológico com apresentação de perfis nutricionais distritais. Edit INDC, 1988. Google Scholar

  • 43.

    Graça MJ, Matias Dias C. The National Health Interview Surveys. History, methods and results. Lisboa: Instituto Nacional de Saúde, 2002. Google Scholar

  • 44.

    Ministério da Saúde. Inquérito Nacional de Saúde 1998/99. INSA-ONSA, 2001. Google Scholar

  • 45.

    Carmo I. Obesidade: epidemia global. Rev Fac Med Lisboa Ser III 2001; 6(Suppl 1): 39–46. Google Scholar

About the article

Corresponding author: Aidil Fonseca, Instituto Nacional de Saúde Dr. Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisboa, Portugal Phone: +351-21-7519-444, Fax: +351-21-752-6400,

Received: 2005-02-21

Accepted: 2005-07-19

Published Online: 2005-09-22

Published in Print: 2005-09-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 43, Issue 9, Pages 907–912, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.155.

Export Citation

©2005 by Walter de Gruyter Berlin New York.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Luis Ruano, Natália Araújo, Mariana Branco, Rui Barreto, Sandra Moreira, Ricardo Pais, Vítor Tedim Cruz, Nuno Lunet, and Henrique Barros
American Journal of Alzheimer's Disease & Other Dementias®, 2018, Page 153331751881355
Mafalda Raposo, Paul Sousa, Stefan Nemeth, Ana Rita Couto, Margarida Rodrigues Santos, João Paulo Pinheiro, Maria João Peixoto, Christian Oberkanins, Nadiya Kazachkova, Teresa Cymbron, Manuela Lima, and Jácome Bruges-Armas
Open Journal of Genetics, 2011, Volume 01, Number 03, Page 48
Mafalda S. Melo, Leticia Balanco, Claudia C. Branco, and Luisa Mota-Vieira
Annals of Human Biology, 2015, Volume 42, Number 3, Page 285
Sarah Egert, Gerald Rimbach, and Patricia Huebbe
Proceedings of the Nutrition Society, 2012, Volume 71, Number 03, Page 410
Fernando José Abelha, Vera Fernandes, Miguela Botelho, Patricia Santos, Alice Santos, J. C. Machado, and Henrique Barros
Journal of Anesthesia, 2012, Volume 26, Number 3, Page 412
Steffen Heide, Kleiber Manfred, Christiane Gläser, and Susanne Schulz
Forensic Science International, 2009, Volume 192, Number 1-3, Page 62
Teresa Cymbron, Mafalda Raposo, Nadiya Kazachkova, Conceição Bettencourt, Francisca Silva, Cristina Santos, Yahya Dahmani, Paula Lourenço, Rita Ferin, Maria Leonor Pavão, and Manuela Lima
Annals of Human Biology, 2011, Volume 38, Number 3, Page 354

Comments (0)

Please log in or register to comment.
Log in