title: Comprehensive genetic analysis of the dipeptidyl peptidase-4 gene and cardiovascular disease risk factors in obese individuals.
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/m(2)) 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.
authors.affiliation: Lipid Research Center, Laval University, 2705 Laurier Blvd (TR93), Quebec City, QC, Canada G1V 4G2.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
authors.forename: Geneviève
authors.initials: G
authors.lastname: Faucher
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Stéfane
authors.initials: S
authors.lastname: Lebel
authors.forename: Frédéric-Simon
authors.initials: FS
authors.lastname: Hould
authors.forename: Picard
authors.initials: P
authors.lastname: Marceau
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D003971:Diastole; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D054795:Incretins / Q000097:blood; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D009767:Obesity, Morbid / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000601:surgery; D011110:Polymorphism, Genetic; D011792:Quebec / Q000453:epidemiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D054795:Incretins; D008055:Lipids; D008074:Lipoproteins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4