Skip to main content
SpringerLink
Log in

Apolipoprotein A5-1131T>C polymorphism, but not APOE genotypes, increases susceptibility for dyslipidemia in children and adolescents

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Apolipoprotein A5 (APOA5) and apolipoprotein E (APOE) play important roles in the metabolism of cholesterol and triglycerides. The aim of this study was to determine the allelic and genotypic distributions of the APOA5-1131T>C (rs 662799) and the APOE HhaI polymorphisms and to identify the association of both individual and combined APOA5–APOE genetic variants and the risk for dyslipidemia in children and adolescents. We genotyped 53 dyslipidemic and 77 normolipidemic individuals. The total cholesterol, triglycerides and HDL cholesterol were determined enzymatically. For APOA5 polymorphism, the presence of the allele C confers an individual risk for dyslipidemia (OR = 2.38, 95% CI = 1.15–4.89; P = 0.018). No significant differences were observed for lipid parameters among the APOA5 groups, except for a higher value of HDLc (P = 0.024) in C-carriers. The allelic and genotypic frequencies of APOE polymorphism were similar between groups and did not increase the susceptibility for dyslipidemia. None of the combined APOA5–APOE polymorphisms increased risk for dyslipidemia. We demonstrated an association between APOA5-1131T>C polymorphism and dyslipidemia in children and adolescents. This finding may be useful to guide new studies with genetic markers down a path toward a better characterization of the genetic risk factors for dyslipidemia and atherosclerotic diseases.

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. Frohlich J, Dobiásová M (2003) Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography. Clin Chem 49:1873–1880

    Article  PubMed  CAS  Google Scholar 

  2. Mendes-Lana A, Pena GG, Freitas SN et al (2007) Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto study. Braz J Med Biol Res 40:49–56

    Article  PubMed  CAS  Google Scholar 

  3. American Heart Association NCEP (2004) Report implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 110:227–239

    Article  Google Scholar 

  4. Baigent C, Keech A, Kearney PM et al (2005) Cholesterol treatment trialists’ (C-FF) collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90, 056 participants in 14 randomized trials of statins. Lancet 366:267–278

    Article  Google Scholar 

  5. Pennacchio LA, Olivier M, Hubacek JA et al (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173

    Article  PubMed  CAS  Google Scholar 

  6. Volcik KA, Barkley RA, Hutchinson RG et al (2006) Apolipoprotein E polymorphisms predict low-density lipoprotein cholesterol levels and carotid artery wall thickness but not incident coronary heart disease in 12,491 ARIC study participants. Am J Epidemiol 164:342–348

    Article  PubMed  Google Scholar 

  7. Kluger M, Heeren J, Merkel M (2008) Apoprotein A–V: an important regulator of triglyceride metabolism. J Inherit Metab Dis 31:281–288

    Article  CAS  Google Scholar 

  8. Tai ES, Ordovas JM (2008) Clinical significance of apolipoprotein A5. Curr Opin Lipidol 19:349–354

    Article  PubMed  CAS  Google Scholar 

  9. Van Der Vliet HN, Sammels MG, Leegwater AC et al (2001) Apolipoprotein AV: a novel apolipoprotein associated with an early phase of liver regeneration. J Biochem 276:44512–44520

    Google Scholar 

  10. Pennacchio LA, Olivier M, Hubacek RM et al (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 11:3031–3038

    Article  PubMed  CAS  Google Scholar 

  11. Ribalta J, Figuera L, Fernandez-Ballart J et al (2002) Newly identified apolipoprotein AV gene predisposes to high plasma triglycerides in familial combined hyperlipidemia. Clin Chem 48:1597–1600

    PubMed  CAS  Google Scholar 

  12. Talmud PJ, Hawe E, Martin S et al (2002) Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet 11:3039–3046

    Article  PubMed  CAS  Google Scholar 

  13. Horinek A, Vrablik M, Ceska R, Adámková V, Poledne R, Kubacek JA (2003) C-polymorphism within the apolipoprotein A–V gene in hypertriglyceridemic individuals. Atherosclerosis 167:369–370

    Article  PubMed  CAS  Google Scholar 

  14. Sousa MO, Alía P, Pintó X, Corbella E, Navarro MA (2008) Interaction between APOA5–1131T>C and APOE polymorphisms and their association with severe hypertriglyceridemia. Clin Chim Acta 395:68–71

    Article  PubMed  CAS  Google Scholar 

  15. AshokKumar M, Subhashini N, SaiBabu R, Ramesh A, Cherian KM, Emmanuel C (2010) Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians. Mol Biol Rep 37:521–527

    Article  PubMed  CAS  Google Scholar 

  16. Hubacek JA, Adamkova V, Prusikova M, Snejdrlova M et al (2009) Impact of apolipoprotein A5 variants on statin treatment efficacy. Pharmacogenomics 10:945–950

    Article  PubMed  CAS  Google Scholar 

  17. Eichner JE, Dunn ST, Perveen G et al (2002) Apolipoprotein E polymorphism and cardiovascular disease: a huge review. Am J Epidemiol 155:487–495

    Article  PubMed  Google Scholar 

  18. Fuzikawa AK, Peixoto SV, Taufer M, Moriguchi EH, Lima-Costa MF (2008) Association of ApoE polymorphisms with prevalent hypertension in 1406 older adults: the Bambuí health aging study (BHAS). Braz J Med Biol Res 41:89–4194

    PubMed  CAS  Google Scholar 

  19. Baroni MG, Berni A, Romeo S et al (2003) Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD. BMC Med Genet 4:962–968

    Article  Google Scholar 

  20. Hu P, Qin Y, Jing C, Lu L, Hu B, Du P (2010) Does the geographical gradient of apoe4 allele exist in china? A systemic comparison among multiple Chinese populations. Mol Biol Rep. doi:10.1007/s11033-010-0132-0

    Google Scholar 

  21. Mahfouz R, Sabbagh A, Zahed L et al (2006) Apolipoprotein E gene polymorphism and allele frequencies in the Lebanese population. Mol Biol Rep 33:145–149

    Article  PubMed  CAS  Google Scholar 

  22. Al-Khedhairy A (2004) Apolipoprotein E polymorphism in Saudis. Mol Biol Rep 31:257–260

    Article  PubMed  CAS  Google Scholar 

  23. Mozas P, Castillo S, Reyes G et al (2003) Apolipoprotein E genotype is not associated with cardiovascular disease in heterozygous subjects with familial hypercholesterolemia. Am Heart J 145:999–1005

    Article  PubMed  CAS  Google Scholar 

  24. Vaisi-Raygani A, Rahimi Z, Tavilani H, Pourmotabbed T (2010) Butyrylcholinesterase k variant and the apoe-epsilon 4 allele work in synergy to increase the risk of coronary artery disease especially in diabetic patients. Mol Biol Rep 37:2083–2091

    Article  PubMed  CAS  Google Scholar 

  25. Bertolini S, Pisciotta L, di Scala L et al (2004) Genetic polymorphisms affecting the phenotypic expression of familial hypercholesterolemia. Atherosclerosis 174:57–65

    Article  PubMed  CAS  Google Scholar 

  26. Sousa MO, Corbella E, Alía P, Cámara J, Castro MJ, Pinto X, Navarro MA (2008) Ausência de associación entre el genótipo de la apolipoproteina E y la respuesta al tratamiento com estatinas em los pacientes com episódios isquêmicos agudos. Med Clin (Barc) 130:401–404

    Article  Google Scholar 

  27. Rahimi Z, Vaisi-Raygani A, Pourmotabbed T (2010) Association between apolipoprotein epsilon4 allele, factor V Leiden, and plasma lipid and lipoprotein levels with sickle cell disease in southern iran. Mol Biol Rep. doi:10.1007/s11033-010-0157-4

    Google Scholar 

  28. Li Y, Tang K, Zhang Z et al. (2010) Genetic diversity of the apolipoprotein E gene and diabetic nephropathy: a meta-analysis. Mol Biol Rep. doi:10.1007/s11033-010-9999-z

    Google Scholar 

  29. Hubacek JA, Horinek A, Skodova Z, Adamkova V, Poledne R (2007) Sex specific interaction between APOE and APOA5 variants and determination of plasma lipid levels. Eur J Hum Genet 16:135–138

    Article  PubMed  Google Scholar 

  30. SBC-Brazilian Society of Cardiology (2005) I Guidelines for the prevention of atherosclerosis in childhood and adolescence. Arq Bras Cardiol 85:4–36

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  32. Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31:545–548

    PubMed  CAS  Google Scholar 

  33. Parra FC, Amado RC, Lambertucci JR, Rocha J, Antunes CM, Pena SDJ (2003) Color and genomic ancestry in Brazilians. Proc Natl Acad Sci 100:177–182

    Article  PubMed  CAS  Google Scholar 

  34. Evans D, Buchwald A, Beil FU (2003) The single nucleotide polymorphism −1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipemia. J Mol Med 81:645–654

    Article  PubMed  CAS  Google Scholar 

  35. Moreno-Luna R, Perez-Jimenez F, Marin C et al (2007) Two independent apolipoprotein A5 haplotypes module post-prandial lipoprotein metabolism in a healthy Caucasian population. J Endocrin Metab 92:2280–2285

    Article  CAS  Google Scholar 

  36. Nabika T, Nasreen S, Kobayashi S, Masuda J (2002) The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese. Atherosclerosis 165:201–204

    Article  PubMed  CAS  Google Scholar 

  37. Bi N, Yan SK, Li GP, Yin ZN, Chen BS (2004) A single nucleotide polymorphism −1131T>C in the apolipoprotein A5 gene is associated with a increased risk of coronary artery disease and alters triglyceride metabolism in Chinese. Mol Genet Metab 83:280–286

    Article  PubMed  CAS  Google Scholar 

  38. Hsu LA, Ko YL, Chang CJ et al (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  PubMed  CAS  Google Scholar 

  39. Matsunaga A, Arishima H, Nijmura H et al (2007) Strong linkage disequilibrium and association of −1131T>C and c.553G>T polymorphisms of the apolipoprotein A5 gene with hypertriglyceridemia in a Japanese population. Circ J 71:746–752

    Article  PubMed  CAS  Google Scholar 

  40. Pitsavos C, Choumerianou DM, Skoumas J et al (2005) Apolipoprotein E polymorphism is not associated with lipid levels and coronary artery disease in Greek patients with familial hypercholesterolemia. Clin Exp Med 5:196–201

    Article  PubMed  CAS  Google Scholar 

  41. Giassakis G, Veletza S, Papanas N, Heliopoulos I, Piperidou H (2007) Apolipoprotein E and first-ever ischaemic stroke in Greek hospitalized patients. J Int Med Res 35:127–133

    PubMed  CAS  Google Scholar 

  42. Grönroos P, Raitakari OT, Kähönen M et al (2007) Influence of apolipoprotein E polymorphism on serum lipid and lipoprotein chances: a 21-year follow-up study from childhood to adulthood. The cardiovascular risk in young Finns study. Clin Chem Lab Med 45:592–598

    Article  PubMed  Google Scholar 

  43. Fuzikawa AK, Peixoto SV, Taufer M, Moriguchi EH, Lima-Costa MF (2007) Apolipoprotein E polymorphism distribution in an elderly Brazilian population: the Bambuí health and aging study. Braz J Med Biol Res 40:1429–1434

    Article  PubMed  CAS  Google Scholar 

  44. Bazrgar M, Karimi M, Fathzadeh M et al (2008) Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts. Mol Biol Rep 35:495–499

    Article  PubMed  CAS  Google Scholar 

  45. França E, Alves JGB, Hutz MH (2004) Apolipoprotein E polymorphism and its association with serum lipid levels in Brazilian children. Hum Biol 76:267–275

    Article  PubMed  Google Scholar 

  46. Fiegenbaum M, Andrade FM, Hutz MH (2007) Association between plasma lipid parameters and APOC3 genotypes in Brazilian subjects: effect of gender, smoking and APO E genotypes. Clin Chim Acta 380:175–181

    Article  PubMed  CAS  Google Scholar 

  47. Svobodová H, Kucera F, Stulc T et al (2007) Apolipoprotein E gene polymorphism in the Mongolian population. Folia Biol (Praha) 53:138–142

    Google Scholar 

  48. Granér M, Kahri J, Varpula M et al (2008) Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease. Nutr Metab Cardiovasc Dis 18:271–277

    Article  PubMed  Google Scholar 

  49. Saidi S, Slamia LB, Ammou SB, Mahjoub T, Almawi WY (2007) Association of apolipoprotein E gene polymorphism with ischemic stroke involving large-vessel disease and its relation to serum lipid levels. J Stroke Cerebrovasc Dis 16:160–166

    Article  PubMed  Google Scholar 

  50. Jang Y, Paik JK, Hyun JY et al (2009) The apolipoprotein A5–1131T>C promoter polymorphism in Koreans: association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease. Clin Chim Acta 402:83–87

    Article  PubMed  CAS  Google Scholar 

  51. Endo K, Yanagi H, Araki J, Hirano C, Yamakawa-Kobayashi K, Tomura S (2002) Association found between the promoter region polymorphism in the apolipoprotein A–V gene and the serum triglyceride level in Japanese schoolchildren. Hum Genet 111:570–572

    Article  PubMed  CAS  Google Scholar 

  52. Charriere S, Bernard S, Aqallal M et al (2008) Association of APOA5–1131T>C and S19 W gene polymorphisms with both mild hypertriglyceridemia and hyperchylomicronemia in type 2 diabetic patients. Clin Chim Acta 394:99–103

    Article  PubMed  CAS  Google Scholar 

  53. Srinivasan SR, Ehnholm C, Wattigney W, Berenson GS (1993) Apolipoprotein E polymorphism and its association with serum lipoprotein concentrations in black versus white children: the Bogalusa Heart Study. Metabolism 42:381–386

    Article  PubMed  CAS  Google Scholar 

  54. Callas N, Poveda E, Baracaldo C, Hernández P, Castillo C, Guerra M (2007) Polimorfismo genético de la apolipoproteína E en un grupo de escolares del centro-oriente colombiano: comparación con las concentraciones plasmáticas de lípidos y apolipoproteínas. Biomédica 27:526–536

    PubMed  Google Scholar 

  55. Souza DRS, Nakachima L, Biagioni RB et al (2007) Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coronary artery disease. Braz J Med Biol Res 40:189–197

    Article  PubMed  CAS  Google Scholar 

  56. Liang S, Pan M, Geng H et al (2009) Apolipoprotein E polymorphism in normal Han Chinese population: frequency and effect on lipid parameters. Mol Biol Rep 36:1251–1256

    Article  PubMed  CAS  Google Scholar 

  57. Hagberg JM, Wilund KR, Ferrel R (2000) APOE gene and gene-environment effects on plasma lipoprotein-lipid levels. Physiol Genomics 4:101–104

    PubMed  CAS  Google Scholar 

  58. Schaefer JR, Sattler AM, Hackler B et al (2004) Hyperlipidemia in patients with apolipoprotein E2/E2 phenotype: apolipoprotein A5 S19 W mutation as a cofactor. Clin Chem 50:2214

    Article  PubMed  CAS  Google Scholar 

  59. Hubacek JA, Horinek A, Skodova Z et al (2005) Hypertriglyceridemia: interaction between APOE POA5 variants. Clin Chem 51:1311–1313

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We acknowledge the Conselho Nacional de Desenvolvimento Científico e Tecnológico-(CNPq, Brazil) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil) for financial support. We thank Dr. Ennio Leão, Dr. Viviane Cássia Kanufre, Dr. Mayumi Kanashiro and Dr. Adriana Brasil (Clinical Hospital of UFMG); José Oswaldo and Zilda (Central Laboratory of the Clinical Hospital of UFMG); Fátima, Márcio and Eunice (Department of Clinical and Toxicological Analysis of the Faculty of Pharmacy of UFMG); Carminha and Raquel (Pedagogic Centre of UFMG); and Edeuvanis (from Alcindo Vieira School).

Author information

Authors and Affiliations

  1. Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Antônio Carlos avenue, 6627, Belo Horizonte, MG, 31270-901, Brazil

    D. D. V. Brito, A. P. Fernandes, K. B. Gomes, F. F. Coelho, N. G. Cruz, A. P. Sabino, J. E. Cardoso & M. O. Sousa

  2. São Vicente de Paulo Ambulatory Pediatrics, Clinical Hospital of Federal University of Minas Gerais, Belo Horizonte, Brazil

    P. P. Figueiredo-Filho, R. Diamante & C. R. Norton

  3. Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil

    D. D. V. Brito

Authors
  1. D. D. V. Brito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. P. Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. B. Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. F. Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. G. Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. P. Sabino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. E. Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. P. Figueiredo-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R. Diamante
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. R. Norton
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. O. Sousa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. B. Gomes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brito, D.D.V., Fernandes, A.P., Gomes, K.B. et al. Apolipoprotein A5-1131T>C polymorphism, but not APOE genotypes, increases susceptibility for dyslipidemia in children and adolescents. Mol Biol Rep 38, 4381–4388 (2011). https://doi.org/10.1007/s11033-010-0565-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0565-5

Keywords

Search

Navigation