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 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.

Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: the DIABHYCAR prospective study.

AIM: Vitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients. METHODS: A cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 ± 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI). RESULTS: In the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05-1.29; P = 0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P = 0.04) alleles and baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02-1.28; P = 0.04). In a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P = 0.009) and TaqI (P = 0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03-1.73; P = 0.03). CONCLUSION: The haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors.