Acta Diabetologica

, Volume 46, Issue 1, pp 13–21 | Cite as

Comprehensive genetic analysis of the dipeptidyl peptidase-4 gene and cardiovascular disease risk factors in obese individuals

  • Luigi Bouchard
  • Geneviève Faucher
  • André Tchernof
  • Yves Deshaies
  • Stéfane Lebel
  • Frédéric-Simon Hould
  • Picard Marceau
  • Marie-Claude Vohl
Original Article

Abstract

The incretin system has been shown to stimulate insulin secretion in a glucose dependent manner and currently fosters considerable hope for the treatment of diabetes. Recently, we have shown that the dipeptidylpeptidase-4 (DPP4) gene, which is responsible for incretin inactivation, was overexpressed in omental adipose tissue of obese men with the metabolic syndrome, compared to men not characterized by this condition. Since the cardiovascular disease (CVD) risk profile shows substantial inter-individual variability in obesity, this study aimed at verifying whether DPP4 polymorphisms contribute to explain such a difference. In the first step of this multi-stage study, seven tagging SNPs were genotyped in a sample of 576 obese (BMI > 40 kg/m2) individuals and tested for their association with blood pressure and lipids, as well as diabetes-related phenotypes. Then, in an additional sample of 572 obese individuals (stage 2), SNPs showing trends (P < 0.10) for an association in the first sample were genotyped and reanalyzed. Logistic regressions were used to compute odds ratio for obesity-related metabolic complications. In sample 1, homozygotes for rs17848915 and rs7608798 minor alleles were at lower risk of hyperglycemia/diabetes (P = 0.002) and elevated plasma triglyceride levels (P = 0.030) respectively, whereas rs1558957 heterozygotes were at higher risk to have high plasma triglyceride (P = 0.040), HDL- (P = 0.021), LDL- (P = 0.001) and total-cholesterol (P = 0.003) levels. However, none of these associations was consistently replicated in stage 2. This first comprehensive genetic analysis does not support the notion that DPP4 polymorphisms could modulate the CVD risk profile among obese patients.

Keywords

Metabolic syndrome Diabetes Candidate gene Polymorphism Association study 

Notes

Acknowledgments

This study was supported by a grant from the Canadian Institutes of Health Research (CIHR) and the Institute of Nutrition, Metabolism and Diabetes (INMD) under its strategic initiative “‘Excellence, Innovation and Advancement in the Study of Obesity and Healthy Body Weight.” The morbidly obese cohort was supported, over the years, by the Laval University Merck Frosst/CIHR Research Chair in Obesity. We express our gratitude to Drs Simon Marceau, Odette Lescelleur, Simon Biron, members of the Laval Hospital biliopancreatic diversion team, who have also sampled adipose tissues for this project. Many thanks are also expressed to Dr Fanny Therrien and Alain Houde, M.Sc., for their help in adipose tissue banking management. We acknowledge the contribution of the Gene Quantification core laboratory of the Centre de Génomique de Québec. Dr Luigi Bouchard is funded by the Laval University Merck Frosst/CIHR Research Chair in Obesity and the Heart and Stroke Foundation of Canada (HSFC)/Sanofi-Aventis research fellowship awards. Dr. André Tchernof is a research scholar from CIHR.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Luigi Bouchard
    • 1
    • 2
    • 3
  • Geneviève Faucher
    • 1
    • 2
    • 3
  • André Tchernof
    • 2
    • 3
    • 4
  • Yves Deshaies
    • 5
  • Stéfane Lebel
    • 6
  • Frédéric-Simon Hould
    • 6
  • Picard Marceau
    • 6
  • Marie-Claude Vohl
    • 1
    • 2
    • 3
  1. 1.Lipid Research CenterLaval UniversityQuebec CityCanada
  2. 2.Nutraceuticals and Functional Foods InstituteLaval UniversityQuebec CityCanada
  3. 3.Department of Food Science and NutritionLaval UniversityQuebec CityCanada
  4. 4.Molecular Endocrinology and Oncology Research CenterLaval UniversityQuebec CityCanada
  5. 5.Department of Anatomy and Physiology and Laval Hospital Research CenterLaval UniversityQuebec CityCanada
  6. 6.Department of Surgery, Faculty of MedicineLaval UniversityQuebec CityCanada

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