Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Effect of obesity on HDL and LDL particle sizes in carriers of the null P207L or defective D9N mutation in the lipoprotein lipase gene: the Québec LipD Study

Abstract

BACKGROUND: We have recently demonstrated that French Canadians bearing a mutation in the lipoprotein lipase (LPL) gene present an impaired lipoprotein–lipid profile characterized by small low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles compared with healthy subjects. It has also been documented that obesity has a significant impact on HDL and LDL particle sizes.

OBJECTIVE: To examine the extent to which obesity modulates HDL and LDL particle sizes among carriers of mutations in the LPL gene.

SUBJECTS:Analyses were carried out in 206 heterozygous carriers of the D9N mutation (N=118) or the P207L mutation (N=88).

MEASUREMENTS: Lipoprotein particle sizes were measured on whole plasma by nondenaturing polyacrylamide gradient gel electrophoresis.

RESULTS: In general, body mass index (BMI) and waist circumference were significant correlates of LDL and HDL particle sizes among heterozygous carriers of the P207L or D9N mutation in the LPL gene, with relatively similar associations among men and women. Multivariate analyses indicated that variations in waist circumference but not BMI were an independent predictor of variations in both HDL particle size (5.2%, P=0.0005) and LDL particle size (5.9%, P=0.01) in the entire group of heterozygotes for LPL mutation in a model that included the nature of the LPL mutation (D9N vs P207L), gender, age, cholesterol and plasma TG levels. Interestingly, there was a significant interaction between plasma TG levels and waist circumference or BMI in modulating HDL particle size. Indeed, an increased waist circumference or BMI was associated with a significant reduction in HDL particle size among subjects with plasma TG levels ≤3.5 mmol/l, but not among those with marked hypertriglyceridemia (TG levels >3.5 mmol/l).

CONCLUSION: These results suggest that abdominal obesity, more so that overall obesity, is an important determinant of variations in LDL and HDL particle size among heterozygous carriers of mutations in the LPL gene, perhaps further contributing to modulate the risk of CHD in these individuals.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Despres JP, Pascot A, Lemieux I . Risk factors associated with obesity: a metabolic perspective. Ann Endocrinol 2000; 61 (Suppl 6): 31–38.

    CAS  Google Scholar 

  2. Tchernof A, Lamarche B, Prud'homme D, Nadeau A, Moorjani S, Labrie F, Lupien PJ, Despres JP . The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 1996; 19: 629–637.

    Article  CAS  Google Scholar 

  3. Pascot A, Lemieux I, Prud'homme D, Tremblay A, Nadeau A, Couillard C, Bergeron J, Lamarche B, Despres JP . Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. J Lipid Res 2001; 42: 2007–2014.

    CAS  PubMed  Google Scholar 

  4. Lamarche B, St-Pierre AC, Ruel IL, Cantin B, Dagenais GR, Despres JP . A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men. Can J Cardiol 2001; 17: 859–865.

    CAS  PubMed  Google Scholar 

  5. St-Pierre AC, Ruel IL, Cantin B, Dagenais GR, Bernard PM, Despres JP, Lamarche B . Comparison of various electrophoretic characteristics of LDL particles and their relationship to the risk of ischemic heart disease. Circulation 2001; 104: 2295–2299.

    Article  CAS  Google Scholar 

  6. Gordon T, Castelli W, Hjortland M, Kannel WDT . High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1997; 62: 707–714.

    Article  Google Scholar 

  7. Lamarche B, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Despres JP . Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. Arterioscler Thromb Vasc Biol 1997; 17: 1098–1105.

    Article  CAS  Google Scholar 

  8. Eckel RH . Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 1989; 320: 1060–1068.

    Article  CAS  Google Scholar 

  9. Julien P, Gagne C, Murthy MR, Levesque G, Moorjani S, Cadelis F, Hayden MR, Lupien PJ . Dyslipidemias associated with heterozygous lipoprotein lipase mutations in the French-Canadian population. Hum Mutat. 1998; (Suppl 1): S148–S153.

    Article  Google Scholar 

  10. Monsalve MV, Henderson H, Roederer G, Julien P, Deeb S, Kastelein JJ, Peritz L, Devlin R, Bruin T, Murthy MR . A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries. J Clin Invest 1990; 86: 728–734.

    Article  CAS  Google Scholar 

  11. Ma Y, Henderson HE, Murthy V, Roederer G, Monsalve MV, Clarke LA, Normand T, Julien P, Gagne C, Lambert M . A mutation in the human lipoprotein lipase gene as the most common cause of familial chylomicronemia in French Canadians. N Engl J Med 1991; 324: 1761–1766.

    Article  CAS  Google Scholar 

  12. Ma Y, Wilson BI, Bijvoet S, Henderson HE, Cramb E, Roederer G, Ven MM, Julien P, Bakker HD, Kastelein JJ . A missense mutation (Asp250----Asn) in exon 6 of the human lipoprotein lipase gene causes chylomicronemia in patients of different ancestries. Genomics 1992; 13: 649–653.

    Article  CAS  Google Scholar 

  13. Murthy V, Julien P, Gagne C . Molecular pathobiology of the human lipoprotein lipase gene. Pharmacol Ther 1996; 70: 101–135.

    Article  CAS  Google Scholar 

  14. Hokanson JE . Lipoprotein lipase gene variants and risk of coronary disease: a quantitative analysis of population-based studies. Int J Clin Lab Res 1997; 27: 24–34.

    Article  CAS  Google Scholar 

  15. Hokanson JE . Functional variants in the lipoprotein lipase gene and risk of cardiovascular disease. Curr Opin Lipidol 1999; 10: 393–399.

    Article  CAS  Google Scholar 

  16. Gaudet D, Vohl MC, Julien P, Tremblay G, Perron P, Gagne C, Bergeron J, Moorjani S, Despres JP . Relative contribution of low-density lipoprotein receptor and lipoprotein lipase gene mutations to angiographically assessed coronary artery disease among French Canadians. Am J Cardiol 1998; 82: 299–305.

    Article  CAS  Google Scholar 

  17. Jukema JW, van Boven AJ, Groenemeijer B, Zwinderman AH, Reiber JH, Bruschke AV, Henneman JA, Molhoek GP, Bruin T, Jansen H, Gagne E, Hayden MR, Kastelein JJ . The Asp9 Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary atherosclerosis. REGRESS Study Group, Interuniversity Cardiology Institute, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study. Circulation 1996; 94: 1913–1918.

    Article  CAS  Google Scholar 

  18. Gerdes C, Fisher RM, Nicaud V, Boer J, Humphries SE, Talmud PJ, Faergeman O . Lipoprotein lipase variants D9N and N291S are associated with increased plasma triglyceride and lower high-density lipoprotein cholesterol concentrations: studies in the fasting and postprandial states: the European Atherosclerosis Research Studies. Circulation 1997; 96: 733–740.

    Article  CAS  Google Scholar 

  19. Mailly F, Tugrul Y, Reymer PW, Bruin T, Seed M, Groenemeyer BF, Asplund-Carlson A, Vallance D, Winder AF, Miller GJ . A common variant in the gene for lipoprotein lipase (Asp9-->Asn). Functional implications and prevalence in normal and hyperlipidemic subjects. Arterioscler Thromb Vasc Biol 1995; 15: 468–478.

    Article  CAS  Google Scholar 

  20. Ruel IL, Gaudet D, Perron P, Bergeron J, Julien P, Lamarche B . Characterization of LDL particle size among carriers of a defective or a null mutation in the lipoprotein lipase gene: the Quebec LipD Study. Arterioscler Thromb Vasc Biol. 2002; 22: 1181–1186.

    Article  CAS  Google Scholar 

  21. Ruel IL, Gaudet D, Perron P, Pascot A, Despres JP, Bergeron J, Julien P, Lamarche B . Determinants of HDL particle size in patients with the null (P207L) or defective (D9N) mutation in the lipoprotein lipase gene: the Québec LipD study. Atherosclerosis 2002; 162: 269–276.

    Article  CAS  Google Scholar 

  22. Bijvoet SM, Hayden MR . Mismatch PCR: a rapid method to screen for the Pro207-->Leu mutation in the lipoprotein lipase (LPL) gene. Hum Mol Genet 1992; 1: 541.

    Article  CAS  Google Scholar 

  23. Hall S, Chu G, Miller G, Cruickshank K, Cooper JA, Humphries SE, Talmud PJ . A common mutation in the lipoprotein lipase gene promoter -93T/G, is associated with lower plasma triglyceride levels and increased promoter activity in vitro. Arterioscler Thromb Vasc Biol JID-9505803. 1997; 17: 1969–1976.

    Article  CAS  Google Scholar 

  24. McNamara JR, Schaefer EJ . Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta 1987; 166: 1–8.

    Article  CAS  Google Scholar 

  25. Warnick GR, Benderson J, Albers JJ . Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. Clin Chem 1982; 28: 1379–1388.

    CAS  PubMed  Google Scholar 

  26. Laurell CB . Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45–52.

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  28. Perusse M, Pascot A, Despres JP, Couillard C, Lamarche B . A new method for HDL particle sizing by polyacrylamide gradient gel electrophoresis using whole plasma. J Lipid Res 2001; 42: 1331–1334.

    CAS  PubMed  Google Scholar 

  29. Dietz WH, Foreyt JP, Garrison RJ, Grundy SM, Hansen BC, Higgins M, Hill JO, Howard BV, Kuczmarski RJ, Kumanyika S, Dee Legako R, Prewitt TE, Rocchini AP, Smith PL, Snetselaar LG, Sowers JR, Weintraub M, Williamson DF, Wilson GT, Pi-Sunyer FX . Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res 1998; 6(Suppl 2): S51–S209.

    Article  Google Scholar 

  30. Lemieux S, Prud'homme D, Bouchard C, Tremblay A, Despres JP . A single threshold value of waist girth identifies normal-weight and overweight subjects with excess visceral adipose tissue. Am J Clin Nutr 1996; 64: 685–693.

    Article  CAS  Google Scholar 

  31. Despres JP . Abdominal obesity as important component of insulin-resistance syndrome. Nutrition 1993; 9: 452–459.

    CAS  PubMed  Google Scholar 

  32. Lamarche B, Rashid S, Lewis GF . HDL metabolism in hypertriglyceridemic states: an overview. Clin Chim Acta 1999; 286: 145–161.

    Article  CAS  Google Scholar 

  33. Despres JP, Ferland M, Moorjani S, Nadeau A, Tremblay A, Lupien PJ, Theriault G, Bouchard C . Role of hepatic-triglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women. Arteriosclerosis 1989; 9: 485–492.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Isabelle Ruel is a recipient of a HSFC/CIHR Health Research Partnership Fund. Benoît Lamarche is the recipient of the Canada Research Chair in Nutrition, Functional Foods and Cardiovascular Health. Daniel Gaudet is the holder of the Canada Research Chair in Preventive Genetics and Community Genomics. This research was supported in part by the Fonds de la Recherche en Santé du Québec (FRSQ) and Hydro-Québec.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B Lamarche.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruel, I., Gaudet, D., Perron, P. et al. Effect of obesity on HDL and LDL particle sizes in carriers of the null P207L or defective D9N mutation in the lipoprotein lipase gene: the Québec LipD Study. Int J Obes 27, 631–637 (2003). https://doi.org/10.1038/sj.ijo.0802276

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802276

Keywords

This article is cited by

Search

Quick links