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The present study is the first meta-analysis to evaluate type 2 diabetes (T2D)- associated polymorphisms in cohorts originated from several Tunisian regions. In fact, we evaluated the effect of seven polymorphisms in the following genes—PPARg (Pro12Ala), TNFα (-308A/G), ENPP1(K121Q), TCF7L2(rs7903146°C/T), MTHFR(C677T), ACE(I/D), and CAPN10(3R/2R)—on T2D risk, through a meta-analysis combining data of previous studies performed on Tunisian populations originating from the north, center, or south of the country. R statistics version 2.12.1 software was used to estimate the heterogeneity between studies. Pooled odds ratios were computed by the fixed-effects method of Mantel-Haenszel if no heterogeneity between studies exists. Despite the similarities founded in a number of loci, the Woolf test reported that the contributions of ENPP1 and ACE loci in T2D risk are dependent on the geographic origin of concerned groups, and this heterogeneity could be attributed not only to the variable contribution of the variant in T2D risk but also to diversities of genetic background between tested groups. Interestingly, observed heterogeneity highlighted founding concerning Y chromosome and the mitochondrial DNA about the genetic structure of Tunisian population and proves once again that Tunisians, like the north-Africans, are a mosaic of subpopulations, with significant differences in genetic structure. In homogeneous groups, we replicated the association of single-nucleotide polymorphisms of TCF7L2, MTHFR, CAPN 10, TNFα, and ACE genes with a T2D risk in the Tunisian population with OR ranging from 1.43 to 6.72. However, we reported an absence of the association of PPARg with T2D in the Tunisian population.