In this study, we analyzed five polymorphisms in the following genes, rs7903146 of TCF7L2, rs7923837 of HHEX, rs1788994 of GCK, rs5219 of KCNJ11/Kir6.2 and rs1044498 of ENPP1 using a case-control design in 1,397 individuals (884 unrelated T2D patients and 513 normoglycemic controls) to assess their association with T2D risk in the Tunisian population. The gene discussed is GCK; the disease is type 2 diabetes mellitus.