A Nicolas1, R Aubert2, N Bellili-Muñoz2, B Balkau3, F Bonnet4, J Tichet5, G Velho2, M Marre6, R Roussel7, F Fumeron8. 1. Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France. 2. Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France. 3. Inserm, Centre for Research in Epidemiology and Population Health (CESP), University Paris-Sud, University Versailles Saint-Quentin, UMR-S 1018, 94800 Villejuif, France. 4. Inserm, Centre for Research in Epidemiology and Population Health (CESP), University Paris-Sud, University Versailles Saint-Quentin, UMR-S 1018, 94800 Villejuif, France; Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Rennes, University Rennes 1, 35002 Rennes, France. 5. IRSA, 37520 La Riche, France. 6. Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France; Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, AP-HP, 75018 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France. 7. Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, AP-HP, 75018 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France. 8. Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France. Electronic address: frederic.fumeron@inserm.fr.
Abstract
AIM: Adiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population. METHODS: Two polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n=5212) and people with T2D in the DIABHYCAR study (n=3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n=230), and in controls who remained normoglycaemic (n=226) throughout. RESULTS: In a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04-1.18; P=0.001) and 0.92 (95% CI: 0.87-0.98; P=0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P=0.03) and HbA1c (P=0.006), and lower plasma adiponectin levels (P=0.03) in the D.E.S.I.R. PARTICIPANTS: Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P=0.03), HbA1c (P=0.02) and Fatty Liver Index (FLI; P≤0.01), and higher plasma adiponectin levels (P=0.002). Associations with HbA1c, FLI and adiponectin levels persisted after adjusting for BMI. CONCLUSION: CDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.
AIM: Adiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population. METHODS: Two polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n=5212) and people with T2D in the DIABHYCAR study (n=3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n=230), and in controls who remained normoglycaemic (n=226) throughout. RESULTS: In a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04-1.18; P=0.001) and 0.92 (95% CI: 0.87-0.98; P=0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P=0.03) and HbA1c (P=0.006), and lower plasma adiponectin levels (P=0.03) in the D.E.S.I.R. PARTICIPANTS: Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P=0.03), HbA1c (P=0.02) and Fatty Liver Index (FLI; P≤0.01), and higher plasma adiponectin levels (P=0.002). Associations with HbA1c, FLI and adiponectin levels persisted after adjusting for BMI. CONCLUSION:CDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.