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

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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.

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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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Authors and Affiliations

  1. Lipid Research Center, Laval University, 2705 Laurier Blvd (TR93), Quebec City, QC, Canada, G1V 4G2

    Luigi Bouchard, Geneviève Faucher & Marie-Claude Vohl

  2. Nutraceuticals and Functional Foods Institute, Laval University, Quebec City, QC, Canada

    Luigi Bouchard, Geneviève Faucher, André Tchernof & Marie-Claude Vohl

  3. Department of Food Science and Nutrition, Laval University, Quebec City, QC, Canada

    Luigi Bouchard, Geneviève Faucher, André Tchernof & Marie-Claude Vohl

  4. Molecular Endocrinology and Oncology Research Center, Laval University, Quebec City, QC, Canada

    André Tchernof

  5. Department of Anatomy and Physiology and Laval Hospital Research Center, Laval University, Quebec City, QC, Canada

    Yves Deshaies

  6. Department of Surgery, Faculty of Medicine, Laval University, Quebec City, QC, Canada

    Stéfane Lebel, Frédéric-Simon Hould & Picard Marceau

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  1. Luigi Bouchard
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  2. Geneviève Faucher
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  3. André Tchernof
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  4. Yves Deshaies
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  5. Stéfane Lebel
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  6. Frédéric-Simon Hould
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  7. Picard Marceau
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  8. Marie-Claude Vohl
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Correspondence to Marie-Claude Vohl.

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Bouchard, L., Faucher, G., Tchernof, A. et al. Comprehensive genetic analysis of the dipeptidyl peptidase-4 gene and cardiovascular disease risk factors in obese individuals. Acta Diabetol 46, 13–21 (2009). https://doi.org/10.1007/s00592-008-0049-4

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  • DOI: https://doi.org/10.1007/s00592-008-0049-4

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