STAT4 is not associated with type 2 diabetes in the genetically homogeneous population of Crete

Current classifications of diabetes distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D). However, recent evidence highlights overlap between T1D and T2D. In a recent study, we have suggested for the first time that STAT4 gene polymorphism is associated with increased risk for the development of T1D in the island of Crete, a well-defined area with genetically homogeneous population. The objective of this study was to investigate the putative association of STAT4 polymorphism with T2D. STAT4 encodes a transcription factor that transmits signals induced by several key cytokines, including interleukin-12 (IL-12) and interferon-gamma, a key indicator of T-cell differentiation into type 1 helper T (Th1) cells. Mutated allele T was more common in controls than in individuals with T2D (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.022-2.470, p = 0.039). Mutated genotype G/T was more common in nondiabetic individuals than in T2D patients (OR = 1.735, 95% CI = 1.077-2.793, p = 0.024). Our results indicate that whilst allele T of the STAT4 rs7574865 gene polymorphism is associated with susceptibility to T1D, it is not associated with increased risk for and T2D, and thus does not represent a common genetic factor for diabetes.