Genetic Susceptibility to Type 2 Diabetes: A Global Meta-Analysis Studying the Genetic Differences in Tunisian Populations

Abstract

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), CAPN10(3R/2R) on T2D risk, through a meta-analysis combining data of previous studies performed on Tunisian populations originating from the north, centre or south of the country. R statistics version 2.12.1 software was used to estimate the heterogeneity between studies. Pooled ORs 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 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 homogenous groups, we replicated the association of SNPs of TCF7L2, MTHFR, CAPN 10, TNFα and ACE genes with T2D risk in Tunisian population with OR ranging from 1.43 to 6.72. However, we reported an absence of association of PPARg with T2D in Tunisian population.

The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil

“…First, we cannot rule out the possibility of population stratification bias when analyzing our samples, even though only white subjects were studied and both T2DM patients and non-diabetic subjects were recruited from the same hospital, thus reducing the risk of false-positive/negative associations due to this bias. Second, we did not perform a replication of the observed association in another sample from Southern Brazil, although our data is in agreement with the majority of studies performed in different populations (5)(6)(7)(8)31,(36)(37)(38)(39)(40) and also with another Brazilian study (23). Third, we only analyzed one SNP in the TCF7L2 gene.…”

“…The consistency in the data showing the association between TCF7L2 gene variants and risk for T2DM reported by many studies in different populations is believed to be a reliable indicative of a universal contribution of this gene to T2DM development (31), even though some studies have reported weak or no association with the disease, mainly in Asian populations (21,(32)(33)(34)(35). Thus, to date, around 10 meta-analyses evaluated the pooled effect of TCF7L2 rs7903146 SNP in T2DM risk (5)(6)(7)(8)31,(36)(37)(38)(39)(40).…”

The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10,APM1 and FUT6 genes

“…Single-nucleotide polymorphism rs3792267polymorphism in CAPN10 has been examined on the effect of regulating insulin sensitivity and CAPN10 mRNA levels [33]. However, divergent results were reported and gave a heterogeneous picture owing to racial or regional differences [31,32,34,35]. Our study revealed that the A allele of rs3792267 of CAPN10 was significantly associated with T2DM in Uyghur participants (P = 0.002, adjusted for age, gender and BMI) ( Table 2).…”

“…Among the 13 T2DM genetic susceptibility loci screened, we found significant association with T2DM for three of them, i.e., rs3792267 (CAPN10), rs1501299 (APM1) and rs3760776 (FUT6). CAPN10 gene, identified as the first susceptibility gene for T2DM by positional cloning [25], has been associated the increased risk of T2DM in different populations [30][31][32]. It has been well documented that the abnormal expression of CAPN10 in pancreatic islets, muscle and liver is related to insulin secretion and action, and thereby is considered to be an important novel pathway involved in glucose metabolism [25].…”

PPARGC1A rs3736265 G>A polymorphism is associated with decreased risk of type 2 diabetes mellitus and fasting plasma glucose level

“…The peroxisome proliferator-activated receptor gamma (PPARG), an important transcription factor, keep the balance of energy metabolism by promoting either energy dissipation or energy deposition [7]. Recent studies reported that PPARG gene was correlated with higher risk to diabetes [8] and the G allele of the rs1801282 C>G polymorphism in PPARG gene was associated with T2DM rsk in a genome-wide association study (GWAS) [9] and has been replicated in some case-control studies; however, other studes found no association between this polymorphism and T2DM [10–12]. The peroxisome proliferator-activated receptor gamma co-activator 1 (PPARGC1) family (e.g.…”