Skip to main content
SpringerLink
Log in

Dietary fat and apolipoprotein genotypes modulate plasma lipoprotein levels in Brazilian elderly women

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

Abstract

Studies show that genetic polymorphisms in apolipoproteins, which are in charge of lipid transport, predispose to atherogenic dyslipidemia. This study aimed to investigate the impact of apolipoprotein E, A5, and B genotypes and dietary intake on lipid profile in a sample of elderly women in Brazil. Two hundred and fifty-two women (60 years or older) living in the outskirts of the Brazilian Federal District underwent clinical and laboratory assessments to characterize glycemic and lipidemic variables, and also to exclude confounding factors (smoking, drinking, hormone replacement, cognitive impairment, physical activity). Three-day food records were used to determine usual dietary intake, whereas genotypic evaluations were in accordance to established methodologies. Genotype frequencies were consistent with the Hardy–Weinberg equilibrium. Prior to adjustment, individuals carrying the ε2 allele showed higher serum levels of triglycerides (P < 0.05) and VLDL (P < 0.005) compared to ε4 carriers, whereas LDL levels were considerably elevated in ε4 compared to ε2 carriers. In the presence of high intake of total fat or a low ratio of polyunsaturated to saturated fatty acid, ε4 carriers lost protection against hypertriglyceridemia. There was no association of the apolipoprotein A5 and B genotypes with lipidemic levels independently of the fat intake regimen. Results are suggestive of a dysbetalipoproteinemic-like phenotype in postmenopausal women, with remarkable gene–diet interaction.

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

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Ribalta J, Vallve JC, Girona J, Masana L (2003) Apolipoprotein and apolipoprotein receptor genes, blood lipids and disease. Curr Opin Clin Nutr Metab Care 6:177–187

    Article  CAS  PubMed  Google Scholar 

  3. Davignon J, Cohn JS, Mabile L, Bernier L (1999) Apolipoprotein E and atherosclerosis: insight from animal and human studies. Clin Chim Acta 286:115–143

    Article  CAS  PubMed  Google Scholar 

  4. Dallongeville J, Lussier-Cacan S, Davignon J (1992) Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis. J Lipid Res 33:447–454

    CAS  PubMed  Google Scholar 

  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

    PubMed  Google Scholar 

  6. Greenow K, Pearce NJ, Ramji DP (2005) The key role of apolipoprotein E in atherosclerosis. J Mol Med 83:329–342

    Article  CAS  PubMed  Google Scholar 

  7. Hsu LA, Ko YL, Chang CJ, Hu CF, Wu S, Teng MS, Wang CL, Ho WJ, Ko YS, Hsu TS, Lee YS (2006) Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 185:143–149

    Article  CAS  PubMed  Google Scholar 

  8. Szalai C, Keszei M, Duba J, Prohaszka Z, Kozma GT, Csaszar A, Balogh S, Almassy Z, Fust G, Czinner A (2004) Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease. Atherosclerosis 173:109–114

    Article  CAS  PubMed  Google Scholar 

  9. Lai CQ, Demissie S, Cupples LA, Zhu Y, Adiconis X, Parnell LD, Corella D, Ordovas JM (2004) Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study. J Lipid Res 45:2096–2105

    Article  CAS  PubMed  Google Scholar 

  10. Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, Krauss RM, Rubin EM (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173

    Article  CAS  PubMed  Google Scholar 

  11. Schaap FG, Rensen PC, Voshol PJ, Vrins C, van der Vliet HN, Chamuleau RA, Havekes LM, Groen AK, van Dijk KW (2004) ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis. J Biol Chem 279:27941–27947

    Article  CAS  PubMed  Google Scholar 

  12. Merkel M, Loeffler B, Kluger M, Fabig N, Geppert G, Pennacchio LA, Laatsch A, Heeren J (2005) Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase. J Biol Chem 280:21553–21560

    Article  CAS  PubMed  Google Scholar 

  13. Tybjaerg-Hansen A, Nordestgaard BG, Gerdes LU, Humphries SE (1991) Variation of apolipoprotein B gene is associated with myocardial infarction and lipoprotein levels in Danes. Atherosclerosis 89:69–81

    Article  CAS  PubMed  Google Scholar 

  14. Peacock R, Dunning A, Hamsten A, Tornvall P, Humphries S, Talmud P (1992) Apolipoprotein B gene polymorphisms, lipoproteins and coronary atherosclerosis: a study of young myocardial infarction survivors and healthy population-based individuals. Atherosclerosis 92:151–164

    Article  CAS  PubMed  Google Scholar 

  15. Cavalli SA, Hirata MH, Salazar LA, Diament J, Forti N, Giannini SD, Nakandakare ER, Bertolami MC, Hirata RD (2000) Apolipoprotein B gene polymorphisms: prevalence and impact on serum lipid concentrations in hypercholesterolemic individuals from Brazil. Clin Chim Acta 302:189–203

    Article  CAS  PubMed  Google Scholar 

  16. Benn M (2009) Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review. Atherosclerosis 206:17–30

    Google Scholar 

  17. Scartezini M, Zago MA, Chautard-Freire-Maia EA, Pazin-Filho A, Marin-Neto JA, Hotta JK, Nascimento AJ, Dos-Santos JE (2003) The X−X−/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample. Braz J Med Biol Res 36:369–375

    Article  CAS  PubMed  Google Scholar 

  18. Lai CQ, Corella D, Demissie S, Cupples LA, Adiconis X, Zhu Y, Parnell LD, Tucker KL, Ordovas JM (2006) Dietary intake of n-6 fatty acids modulates effect of apolipoprotein A5 gene on plasma fasting triglycerides, remnant lipoprotein concentrations, and lipoprotein particle size: the Framingham Heart Study. Circulation 113:2062–2070

    Article  CAS  PubMed  Google Scholar 

  19. Mendes-Lana A, Pena GG, Freitas SN, Lima AA, Nicolato RL, Nascimento-Neto RM, Machado-Coelho GL, Freitas RN (2007) Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto study. Braz J Med Biol Res 40:49–56

    Article  CAS  PubMed  Google Scholar 

  20. Fuzikawa AK, Peixoto SV, Taufer M, Moriguchi EH, Lima-Costa MF (2008) Association of ApoE polymorphisms with prevalent hypertension in 1406 older adults: the Bambui Health Aging Study (BHAS). Braz J Med Biol Res 41:89–94

    CAS  PubMed  Google Scholar 

  21. Tonet AC, Karnikowski M, Moraes CF, Gomes L, Karnikowski MG, Cordova C, Nobrega OT (2008) Association between the −174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women. Braz J Med Biol Res 41:47–53

    Article  CAS  PubMed  Google Scholar 

  22. Moraes CF, Souza ER, Souza VC, Medeiros EF, Goncalves TF, Toledo JO, Karnikowski M, Gomes L, Karnikowski MG, Cordova C, Nobrega OT (2008) A common polymorphism in the renin angiotensin system is associated with differential outcome of antihypertensive pharmacotherapy prescribed to Brazilian older women. Clin Chim Acta 396:70–75

    Article  CAS  PubMed  Google Scholar 

  23. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  PubMed  Google Scholar 

  24. Brekke MJ, Brekke ML, Quiter ES, Peters JR, Mullis RM, Hunninghake DB (1992) Appropriate days for measuring intake of dietary fat and cholesterol. Ann Nutr Metab 36:318–327

    Article  CAS  PubMed  Google Scholar 

  25. Stuff JE, Garza C, Smith EO, Nichols BL, Montandon CM (1983) A comparison of dietary methods in nutritional studies. Am J Clin Nutr 37:300–306

    CAS  PubMed  Google Scholar 

  26. Luhrmann PM, Herbert BM, Gaster C, Neuhauser-Berthold M (1999) Validation of a self-administered 3-day estimated dietary record for use in the elderly. Eur J Nutr 38:235–240

    Article  CAS  PubMed  Google Scholar 

  27. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  CAS  PubMed  Google Scholar 

  28. Castro-Costa E, Fuzikawa C, Uchoa E, Firmo JO, Lima-Costa MF (2008) Norms for the mini-mental state examination: adjustment of the cut-off point in population-based studies (evidences from the Bambui health aging study). Arq Neuropsiquiatr 66:524–528

    PubMed  Google Scholar 

  29. Philippi ST (2002) Tabela de composição de alimentos: suporte para decisão nutricional. Coronário, São Paulo, p 135

    Google Scholar 

  30. Donohoe GG, Salomaki A, Lehtimaki T, Pulkki K, Kairisto V (1999) Rapid identification of apolipoprotein E genotypes by multiplex amplification refractory mutation system PCR and capillary gel electrophoresis. Clin Chem 45:143–146

    CAS  PubMed  Google Scholar 

  31. Renges HH, Peacock R, Dunning AM, Talmud P, Humphries SE (1992) Genetic relationship between the 3′-VNTR and diallelic apolipoprotein B gene polymorphisms: haplotype analysis in individuals of European and south Asian origin. Ann Hum Genet 56:11–33

    Article  CAS  PubMed  Google Scholar 

  32. Utermann G, Hees M, Steinmetz A (1977) Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man. Nature 269:604–607

    Article  CAS  PubMed  Google Scholar 

  33. Rall SC Jr, Weisgraber KH, Innerarity TL, Mahley RW (1982) Structural basis for receptor binding heterogeneity of apolipoprotein E from type III hyperlipoproteinemic subjects. Proc Natl Acad Sci USA 79:4696–4700

    Article  CAS  PubMed  Google Scholar 

  34. Cohen J (1992) A power primer. Psychol Bull 112:155–159

    Article  CAS  PubMed  Google Scholar 

  35. Galetto R, Albajar M, Polanco JI, Zakin MM, Rodriguez-Rey JC (2001) Identification of a peroxisome-proliferator-activated-receptor response element in the apolipoprotein E gene control region. Biochem J 357:521–527

    Article  CAS  PubMed  Google Scholar 

  36. Hopkins PN, Heiss G, Ellison RC, Province MA, Pankow JS, Eckfeldt JH, Hunt SC (2003) Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National Heart, Lung, and Blood Institute Family Heart Study. Circulation 108:519–523

    Article  PubMed  Google Scholar 

  37. Hopkins PN, Wu LL, Hunt SC, Brinton EA (2005) Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease. J Am Coll Cardiol 45:1003–1012

    Article  CAS  PubMed  Google Scholar 

  38. Institute of Medicine (1998) Dietary reference intakes: a risk assessment model for establishing upper intake levels for nutrients. Institute of Medicine, Washington, DC

    Google Scholar 

  39. Horejsi B, Ceska R (2000) Apolipoproteins and atherosclerosis. Apolipoprotein E and apolipoprotein(a) as candidate genes of premature development of atherosclerosis. Physiol Res 49(Suppl 1):S63–S69

    CAS  PubMed  Google Scholar 

  40. Srivastava RA, Srivastava N, Averna M, Lin RC, Korach KS, Lubahn DB, Schonfeld G (1997) Estrogen up-regulates apolipoprotein E (ApoE) gene expression by increasing ApoE mRNA in the translating pool via the estrogen receptor alpha-mediated pathway. J Biol Chem 272:33360–33366

    Article  CAS  PubMed  Google Scholar 

  41. Mahley RW, Huang Y, Rall SC Jr (1999) Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res 40:1933–1949

    CAS  PubMed  Google Scholar 

  42. Lopez D, Abisambra Socarras JF, Bedi M, Ness GC (2007) Activation of the hepatic LDL receptor promoter by thyroid hormone. Biochim Biophys Acta 1771:1216–1225

    CAS  PubMed  Google Scholar 

  43. Pimenta JR, Zuccherato LW, Debes AA, Maselli L, Soares RP, Moura-Neto RS, Rocha J, Bydlowski SP, Pena SD (2006) Color and genomic ancestry in Brazilians: a study with forensic microsatellites. Hum Hered 62:190–195

    Article  PubMed  Google Scholar 

  44. Nobrega OT, Faleiros VP, Telles JL (2009) Gerontology in the developing Brazil: achievements and challenges in public policies. Geriatr Gerontol Int 9:135–139

    Article  PubMed  Google Scholar 

  45. Karnikowski M, Cordova C, Oliveira RJ, Karnikowski MG, Nobrega OT (2007) Non-alcoholic fatty liver disease and metabolic syndrome in Brazilian middle-aged and older adults. Sao Paulo Med J 125:333–337

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank dieticians Cristiane Urcina Joanna Oliveira Lima, Érika Beatriz Lopes Tavares, Fabíola Reis Sousa, Fernanda Cristina de Jesus Colares-Bento, and Sarah Ricardo Peres da Silveira for gathering nutritional data and assuring adherence to the food registration procedure. Research supported by the National Council for Scientific and Technological Development—CNPq (Grants 484318/2006-3 and 402699/2007-6), by the Federal District Foundation for Research Development—FAPDF (Grants 193.000.309/2007 and 193.000.449/2008) and by the University of Brasília—UnB (DPP/UnB Grant # 01/2009). R.S. Paula received a fellowship from CAPES, and V.C. Sousa received a fellowship from UCB.

Author information

Authors and Affiliations

  1. Postgraduate Program in Gerontology, Catholic University of Brasília (UCB), Q.S. 07, lote 01, EPCT, Águas Claras, Taguatinga, DF, CEP 72030-170, Brazil

    R. S. Paula, V. C. Souza, E. R. Souza, J. O. Toledo & L. Gomes

  2. Postgraduate Program in Medical Sciences, University of Brasília (UnB), Campus Universitário Darcy Ribeiro, Plano Piloto, DF, 70910-900, Brazil

    A. L. Benedet, C. F. Moraes & O. T. Nóbrega

  3. Geriatrics Service, Hospital of the Catholic University of Brasília (HUCB), Brasília, DF, Brazil

    C. F. Moraes & L. Gomes

  4. Biosciences Faculty, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

    C. S. Alho

  5. Postgraduate Program in Physical Education, Catholic University of Brasília (UCB), Brasília, DF, Brazil

    C. Córdova

Authors
  1. R. S. Paula
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. C. Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. L. Benedet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. R. Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. O. Toledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. F. Moraes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. S. Alho
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. Córdova
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. O. T. Nóbrega
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. T. Nóbrega.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paula, R.S., Souza, V.C., Benedet, A.L. et al. Dietary fat and apolipoprotein genotypes modulate plasma lipoprotein levels in Brazilian elderly women. Mol Cell Biochem 337, 307–315 (2010). https://doi.org/10.1007/s11010-009-0313-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0313-0

Keywords

Search

Navigation