T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
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.
A
A
Nicolas
Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France.
R
R
Aubert
Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France.
N
N
Bellili-Muñoz
Inserm, Centre for Research in Epidemiology and Population Health (CESP), University Paris-Sud, University Versailles Saint-Quentin, UMR-S 1018, 94800 Villejuif, France.
B
B
Balkau
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.
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F
Bonnet
IRSA, 37520 La Riche, France.
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J
Tichet
Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France.
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G
Velho
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.
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M
Marre
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.
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R
Roussel
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.
F
F
Fumeron
D052242:Adiponectin / Q000032:analysis; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005234:Fatty Liver / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin
Adiponectin; Body mass index; Fatty Liver Index; Genetic polymorphisms; T-cadherin; Type 2 diabetes