CDK4 IVS4-nt40G-->A and T2D-associated obesity in Italians.

Cell cycle regulators play crucial roles in the preadipocyte proliferation and adipocyte differentiation. Cyclin-dependent kinase 4 (CDK4) mediates with D-type cyclins entry of cells into cell cycle in response to external stimuli. CDK4 plays a role in body weight, adipogenesis, and beta cell proliferation. CDK4 null mice develop type 2 diabetes (T2D). Furthermore, CDK4 variants are associated with obesity-associated tumors/cancer. We aimed at identifying a role of CDK4 IVS4-nt40G --> A variant in T2D-associated obesity (body mass index, BMI > or = 30) by association tests in an Italian T2D subjects dataset. We recruited from Italy 128 unrelated T2D subjects with BMI <30 kg/m(2) and 54 unrelated T2D subjects with BMI > or = 30 kg/m(2). We performed statistical power calculations in our dataset. DNA samples were directly sequenced with specific primers for CDK4 IVS4-nt40G --> A variant. We identified a significant association of the G allele with T2D-associated obesity and of the A allele with T2D-associated BMI < 30. In our study, we found that the CDK4 IVS4-nt40GG genotype is a risk variant for T2D-associated obesity and that the AA genotype is associated with BMI < 30 in T2D. Hence, CDK4 IVS4-nt40A allele is protective and G allele confers risk for obesity in T2D patients. This study should prompt further work aiming at establishing CDK4 role in contributing to human obesity and T2D-associated obesity.