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

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 HbA _1c (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), HbA _1c (P=0.02) and Fatty Liver Index (FLI; P≤0.01), and higher plasma adiponectin levels (P=0.002). Associations with HbA _1c , 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.
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