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. This evidence concerns the gene ENPP1 and type 2 diabetes mellitus.