Skip to main content
SpringerLink
Log in

A carbohydrate-rich diet reduces LDL size in QQ homozygotes for the Gln192Arg polymorphism of the paraoxonase 1 gene

  • Articles
  • Published:
Lipids

Abstract

Paraoxonase 1 (PON 1) is an esterase with antioxidant properties that is present in HDL. Gln192Arg polymorphism (also named Q192R or Q/R) of the PON 1 gene that encodes this protein defines two alleles (Q and R). The R allele has been associated with higher cardiovascular risk. LDL size and susceptibility to oxidation also have been identified as cardiovascular risk factors. Our objective was to determine whether genetic variations in the Gln192Arg polymorphism influence LDL size and susceptibility to oxidation after the consumption of diets with different fat content. In our experiments, the participants (n=98), underwent three 4-wk diets—one, saturated fat-enriched (SAT); another, monounsaturated fat-enriched (MONO); and a third, carbohydrate-enriched (CHO). We observed that LDL were smaller in the QQ group after the CHO diet vs. the SAT (P<0.01) and MONO diets (P<0.03). No differences in LDL size were found in QR/RR subjects. When we analyzed lag time of oxidation of LDL, we found that when carriers of the R allele (QR/RR) received the MONO diet, the lag period of LDL oxidation was longer as compared with the CHO diet. Otherwise, we found no differences in QQ homozygotes when we evaluated the lag time of oxidation of LDL after the three diets. These results suggest that the Gln192Arg polymorphism of the paraoxonase gene influences LDL size and susceptibility to oxidation in response to diet.

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

Abbreviations

apo:

apolipoprotein

BMI:

body mass index

CHD:

coronary heart disease

CHO:

carbohydrate

MONO:

monounsaturated fat

MUFA:

monounsaturated FA

PON 1:

paraoxonase 1

SAFA:

saturated FA

SAT:

saturated fat

References

  1. Mackness, M.I., Arrol, S., and Durrington, P.N. (1991) Paraoxonase Prevents Accumulation of Lipoperoxides in Low-Density Lipoprotein, FEBS Lett. 286, 152–154.

    Article  PubMed  CAS  Google Scholar 

  2. Watson, A.D., Berliner, J.A., Hama, S.Y., La Du, B.N., Faull, K.F., Fogelman, A.M., and Navab, M. (1995) Protective Effect of High Density Lipoprotein Associated Paraoxonase. Inhibition of the Biological Activity of Minimally Oxidized Low Density Lipoprotein, J. Clin. Invest. 96, 2882–2891.

    PubMed  CAS  Google Scholar 

  3. Mackness, B., Mackness, M.I., Durrington, P.N., Arrol, S., Evans, A.E., McMaster, D., Ferrieres, J., Ruidavets, J.B., Williams, N.R., and Howard, A.N. (2000) Paraoxonase Activity in Two Healthy Populations with Differing Rates of Coronary Heart Disease, Eur. J. Clin. Invest. 30, 4–10.

    Article  PubMed  CAS  Google Scholar 

  4. Sutherland, W.H., Walker, R.J., de Jong, S.A., van Rij, A.M., Phillips, V., and Walker, H.L. (1999) Reduced Postprandial Serum Paraoxonase Activity After a Meal Rich in Used Cooking Fat, Arterioscler. Thromb. Vasc. Biol. 19, 1340–1347.

    PubMed  CAS  Google Scholar 

  5. Neuman, M.P., Neuman, H.R., Durante Costas, F., Barrera, V., Tavella, M., Peterson, G., Veroni, H., and Neuman, J. (2000) Postprandial Increase of Lipid Peroxide Products Parallel Reduction of Antioxidant Enzyme Properties, Atheroscler. 151, 262.

    Article  Google Scholar 

  6. Kudchodkar, B.J., Lacko, A.G., Dory, L., and Fungwe, T.V. (2000) Dietary Fat Modulates Serum Paraoxonase 1 Activity in Rats, J. Nutr. 130, 2427–2433.

    PubMed  CAS  Google Scholar 

  7. Scacchi, R., Corbo, R.M., Rickards, O., and De Stefano, G.F. (2003) New Data on the World Distribution of Paraoxonase (PON1 Gln 192→Arg) Gene Frequencies, Hum. Biol. 75, 365–373.

    PubMed  CAS  Google Scholar 

  8. Serrato, M., and Marian, A.J. (1995) A Variant of Human Paraoxonase/Arylesterase (HUMPONA) Gene Is a Risk Factor for Coronary Artery Disease, J. Clin. Invest. 96, 3005–3008.

    Article  PubMed  CAS  Google Scholar 

  9. Mackness, B., Mackness, M.I., Arrol, S., Turkie, W., and Durington, P.N. (1998) Effect of the Human Serum Paraoxonase 55 and 192 Genetic Polymorphisms on the Protection by High Density Lipoprotein Against Low Density Lipoprotein Oxidative Modification, FEBS Lett. 423, 57–60.

    Article  PubMed  CAS  Google Scholar 

  10. Mackness, M.I., Mackness, B., Durrington, P.N., Connelly, P.W., and Hegele, R.A. (1996) Paraoxonase: Biochemistry, Genetics and Relationship to Plasma Lipoproteins, Curr. Opin. Lipidol. 7, 69–76.

    Article  PubMed  CAS  Google Scholar 

  11. Wheeler, J.G., Keavney, B.D., Watkins, H., Collins, R., and Danesh, J. (2004) Four Paraoxonase Gene Polymorphisms in 11212 Cases of Coronary Heart Disease and 12786 Controls: Meta-Analysis of 43 Studies, Lancet 363, 689–695.

    Article  PubMed  CAS  Google Scholar 

  12. Perez-Jimenez, F., Lopez-Miranda, J., and Mata, P. (2002) Protective Effect of Dietary Monounsaturated Fat on Arteriosclerosis: Beyond Cholesterol, Atherosclerosis 163, 385–398.

    Article  PubMed  CAS  Google Scholar 

  13. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) 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) Final Report, Circulation 106, 3143–3421.

    Google Scholar 

  14. Willett, W.C., Sacks, F., Trichopoulou, A., Drescher, G., Ferro-Luzzi, A., Helsing, E., and Trichopoulos, D. (1995) Mediterranean Diet Pyramid: A Cultural Model for Healthy Eating, Am. J. Clin. Nutr. 61, 1402S-1406S.

    PubMed  CAS  Google Scholar 

  15. Desroches, S., and Lamarche, B. (2004) Diet and Low-Density Lipoprotein Particle Size, Curr. Atheroscler. Rep. 6, 453–460.

    PubMed  Google Scholar 

  16. Perez-Martinez, P., Ordovas, J.M., Lopez-Miranda, J., Gomez, P., Marin, C., Moreno, J., Fuentes, F., Fernandez de la Puebla, R.A., and Perez-Jimenez, F. (2003) Polymorphism Exon 1 Variant at the Locus of the Scavenger Receptor Class B Type I Gene: Influence on Plasma LDL Cholesterol in Healthy Subjects During the Consumption of Diets with Different Fat Contents, Am. J. Clin. Nutr. 77, 809–813.

    PubMed  CAS  Google Scholar 

  17. National Cholesterol Education Program (NCEP). (1994) Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II), Circulation 89, 1333–1445.

    Google Scholar 

  18. Human Nutrition Information Service, U.S. Department of Agriculture (1987) Composition of Foods, Agriculture Handbook No. 8, U.S. Government Printing Office, Washington, DC.

    Google Scholar 

  19. Varela, G. (1980) Tablas de Composicion de Alimentos, Consejo Superior de Investigaciónes Científicas, Madrid.

    Google Scholar 

  20. Allain, C.C., Poon, L.S., Chan, C.S., Richmond, W., and Fu, P.C. (1974) Enzymatic Determination of Total Serum Cholesterol, Clin. Chem. 20, 470–475.

    PubMed  CAS  Google Scholar 

  21. Fossati, P., and Prencipe, L. (1982) Serum Triglycerides Determined Colorimetrically with an Enzyme That Produces Hydrogen Peroxide, Clin. Chem. 28, 2077–2080.

    PubMed  CAS  Google Scholar 

  22. Assmann, G., Schriewer, H., Schmitz, G., and Hagele, E.O. (1983) Quantification of High-Density-Lipoprotein Cholesterol by Precipitation with Phosphotungstic Acid/MgCl2, Clin. Chem. 29, 2026–2030.

    PubMed  CAS  Google Scholar 

  23. Friedewald, W.T., Levy, R.I., and Fredrickson, D.S. (1972) Estimation of the concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge, Clin. Chem. 18, 499–502.

    PubMed  CAS  Google Scholar 

  24. Riepponen, P., Marniemi, J., and Rautaoja, T., (1987) Immunoturbidimetric Determination of Apolipoproteins A-1 and B in Serum, Scand. J. Clin. Lab. Invest. 47, 739–744.

    Article  PubMed  CAS  Google Scholar 

  25. Krauss, R., and Blanche, P. (1992) Detection and Quantification of LDL Subfractions, Curr. Opin. Lipidol. 3, 377 (1992).

    Article  CAS  Google Scholar 

  26. Esterbauer, H., Striegl, G., Puhl, H., and Rotheneder, M. (1989) Continuous Monitoring of in vitro Oxidation of Human Low Density Lipoprotein, Free Radic. Res. Commun. 6, 67–75.

    PubMed  CAS  Google Scholar 

  27. Humbert, R., Adler, D.A., Disteche, C.M., Hassett, C., Omiecinski, C.J., and Furlong, C.E. (1993) The Molecular Basis of the Human Serum Paraoxonase Activity Polymorphism, Nat. Genet. 3, 73–76.

    Article  PubMed  CAS  Google Scholar 

  28. Moreno, J.A., Perez-Jimenez, F., Martin, C., Gomez, P., Perez-Martinez, P., Moreno, R., Bellido, C., Fuentes, F., and Lopez-Miranda, J. (2004) The Effect of Dietary Fat on LDL Size Is Influenced by Apolipoprotein E Genotype in Healthy Subjects, J. Nutr. 134, 2517–2522.

    PubMed  CAS  Google Scholar 

  29. Gonzalez-Amieva, A., Lopez-Miranda, J., Fuentes, F., Castro, P., Marin, C., Lopez-Granados, A., Valles, F., and Perez-Jimenez, F. (2000) Genetic Variations of the Apolipoprotein E Gene Determine the Plasma Triglyceride Levels After Heart Transplantation, J. Heart Lung Transplant. 19, 765–770.

    Article  PubMed  CAS  Google Scholar 

  30. Ordovas, J.M., Lopez-Miranda, J., Mata, P., Perez-Jimenez, F., Lichtenstein, A.H., and Schaefer, E.J. (1995) Gene-Diet Interaction in Determining Plasma Lipid Response to Dietary Intervention, Atherosclerosis 118 (Suppl.), S11-S27.

    Article  PubMed  CAS  Google Scholar 

  31. Ordovas, J.M., Lopez-Miranda, J., Perez-Jimenez, F., Rodriguez, C., Park, J.S., Cole, T., and Schaefer, E.J. (1995) Effect of Apolipoprotein E and A-IV Phenotypes on the Low Density Lipoprotein Response to HMG CoA Reductase Inhibitor Therapy, Atherosclerosis 113, 157–166.

    Article  PubMed  CAS  Google Scholar 

  32. Lopez-Miranda, J., Ordovas, J.M., Mata, P., Lichtenstein, A.H., Clevidence, B., Judd, J.T., and Schaefer, E.J. (1994) Effect of Apolipoprotein E Phenotype on Diet-Induced Lowering of Plasma Low Density Lipoprotein Cholesterol, J. Lipid Res. 35, 1965–1975.

    PubMed  CAS  Google Scholar 

  33. Mackness, M.I., Mackness, B., and Durrington, P.N. (2002) Paraoxonase and Coronary Heart Disease, Atheroscler. Suppl. 3, 49–55.

    Article  PubMed  CAS  Google Scholar 

  34. Rantala, M., Silaste, M.L., Tuominen, A., Kaikkonen, J., Salonen, J.T., Alfthan, G., Aro, A., and Kesaniemi, Y.A. (2002) Dietary Modifications and Gene Polymorphisms Alter Serum Paraoxonase Activity in Healthy Women, J. Nutr. 132, 3012–3017.

    PubMed  CAS  Google Scholar 

  35. Sanghera, D.K., Aston, C.E., Saha, N., and Kamboh, M.I. (1998) DNA Polymorphisms in Two Paraoxonase Genes (PONI and PON2) Are Associated with the Risk of Coronary Heart Disease, Am. J. Hum. Genet. 62, 36–44.

    Article  PubMed  CAS  Google Scholar 

  36. Herrmann, S.M., Blanc, H., Poirier, O., Arveiler, D., Luc, G., Evans, A., Marques-Vidal, P., Bard, J.M., and Cambien, F. (1996) The Gln/Arg Polymorphism of Human Paraoxonase (PON 192) Is Not Related to Myocardial Infarction in the ECTIM Study, Atherosclerosis 126, 299–303.

    Article  PubMed  CAS  Google Scholar 

  37. Ikeda, Y., Suehiro, T., Ohsaki, F., Arii, K., Kumon, Y., and Hashimoto, K. (2003) Relationships Between Polymorphisms of the Human Serum Paraoxonase Gene and Insulin Sensitivity in Japanese Patients with Type 2 Diabetes, Diabetes Res. Clin. Pract. 60, 79–85.

    Article  PubMed  CAS  Google Scholar 

  38. Aviram, M., Billecke, S., Sorenson, R., Bisgaier, C., Newton, R., Rosenblat, M., Erogul, J., Hsu, C., Dunlop, C., and La Du, B. (1998) Paraoxonase Active Site Required for Protection Against LDL Oxidation Involves Its Free Sulfhydryl Group and Is Different from That Required for Its Arylesterase/Paraoxonase Activities: Selective Action of Human Paraoxonase Allozymes Q and R, Arterioscler. Thromb. Vasc. Biol. 18, 1617–1624 (1998).

    PubMed  CAS  Google Scholar 

  39. Mackness, B., Durrington, P.N., and Mackness, M.I. (1999) Polymorphisms of Paraoxonase Genes and Low-Density Lipoprotein Lipid Peroxidation, Lancet 353, 468–469.

    Article  PubMed  CAS  Google Scholar 

  40. Tomás, M., Senti, M., Elosua, R., Vila, J., Sala, J., Masia, R., and Marrugat, J. (2001) Interaction Between the Gln-Arg 192 Variants of the Paraoxonase Gene and Oleic Acid Intake as a Determinant of High-Density Lipoprotein Cholesterol and Paraoxonase Activity, Eur. J. Pharmacol. 432, 121–128.

    Article  PubMed  Google Scholar 

  41. Kuremoto, K., Watanabe, Y., Ohmura, H., Shimada, K., Mokuno, H., and Daida, H. (2003) R/R Genotype of Human Paraoxonase (PON1) Is More Protective Against Lipoprotein Oxidation and Coronary Artery Disease in Japanese Subjects, J. Atheroscler. Thromb. 10, 85–92.

    PubMed  CAS  Google Scholar 

  42. Robertson, K.S., Hawe, E., Miller, G.J., Talmud, P.J., and Humphries, S.E. (2003) Human Paraoxonase Gene Cluster Polymorphisms as Predictors of Coronary Heart Disease Risk in the Prospective Northwick Park Heart Study II, Biochim. Biophys. Acta, 1639, 203–212 (2003).

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. C. Aguilera (Chief)

    Present address: Clinical Biochemistry Service, Hospital Universitario Reina Sofía, Cørdoba, Spain

Authors and Affiliations

  1. Lipid and Arteriosclerosis Research Unit, Department of Medicine, Hospital Universitario Reina Sofía, School of Medicine, University of Córdoba, 14004, Córdoba, Spain

    J. Delgado-Lista, F. Perez-Jimenez, E. Gavilan, C. Marin, F. Fuentes, R. A. Fernandez-Puebla, P. Perez-Martinez, J. A. Paniagua, C. Aguilera (Chief) & J. Lopez-Miranda

Authors
  1. J. Delgado-Lista
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Perez-Jimenez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Gavilan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Marin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. Fuentes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. A. Fernandez-Puebla
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Perez-Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. A. Paniagua
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. Aguilera
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. Lopez-Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Lopez-Miranda.

About this article

Cite this article

Delgado-Lista, J., Perez-Jimenez, F., Gavilan, E. et al. A carbohydrate-rich diet reduces LDL size in QQ homozygotes for the Gln192Arg polymorphism of the paraoxonase 1 gene. Lipids 40, 471–476 (2005). https://doi.org/10.1007/s11745-005-1406-0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-005-1406-0

Keywords

Search

Navigation