CDK4 IVS4‐nt40G→A and T2D‐associated obesity in Italians

Abstract

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.

Cycling through metabolism

“…Interestingly, some studies have already shown the potential interest of these analyses. Variants in the CDK4 and in the CDKN1C locus have been associated to type II diabetes, obesity and glucose metabolism in humans (Meenakshisundaram & Gragnoli, 2009; Meenakshisundaram et al, 2009; Nielsen et al, 2005). Larger populations, and a more systematic study using all cell cycle regulators are definitely required.…”

T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

“…We excluded families with identical twins and siblings with uncertain identical paternity. The Italian family dataset has provided useful genetic information in T2D and associated phenotypes 12 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 .…”

Proteasome Modulator 9 Gene SNPs, Responsible for Anti‐Depressant Response, Are in Linkage With Generalized Anxiety Disorder

“…Families with identical twins, siblings with uncertain identical paternity are excluded. This family dataset has provided useful results for gene identification in MODY3, T2D and associated phenotypes (Gragnoli et al, , , , ,, , ; Godart et al, ; Gragnoli, , ; Gragnoli and Cronsell, ,; Meenakshisundaram and Gragnoli, ,; Meenakshisundaram et al, ,).…”