History of settlement of villages from Central Tunisia by studying families sharing a common founder Glycogenosis type III mutation.

Glycogen storage disease type III (GSD III; Cori disease; Forbes disease) is an autosomal recessive inherited metabolic disorder resulting from deficient glycogen debrancher enzyme activity in liver and muscle. In this study, we focused on a single AGL gene mutation p.W1327X in 16 Tunisian patients from rural area surrounding the region of Mahdia in Central Tunisia. This constitutes the largest pool of patients with this mutation ever described. This study was performed to trace the history of the patients' ancestries in a single region. After extraction of genomic DNA, exon 31 of AGL gene was sequenced. The patients were investigated for the hypervariable segment 1 of mitochondrial DNA and 17 Y-STR markers. We found that the p.W1327X mutation was a founder mutation in Tunisia Analysis of maternal lineages shows an admixture of autochthonous North African, sub-Saharan and a predominance of Eurasian haplogroups. Heterogeneity of maternal haplogroups indicates an ancient settlement. However, paternal gene flow was highly homogeneous and originates from the Near East. We hypothesize that the p.W1327X mutation was introduced into the Tunisian population probably by a recent migration event; then the mutation was fixed in a small region due to the high rate of consanguineous marriages and genetic drift. The screening for this mutation should be performed in priority for GSD III molecular diagnosis, for patients from the region of Mahdia and those from regions sharing the same settlement history.

Association of genetic variants in the FTO gene with metabolic syndrome: A case-control study in the Tunisian population.

AIMS: Variants in the fat mass and obesity-associated gene (FTO) are associated with obesity and type 2 diabetes. However, the association of FTO variants in the MENA (Middle East and North Africa) region with MetS is largely unknown. In this study, we aimed to investigate the association of FTO gene with MetS and its components in Tunisian population. METHODS: Two variants in the FTO gene were genotyped: rs1421085 T>C and rs8057044 A>G in cases and controls from Tunisian population. Anthropometric and biochemical parameters were assessed. Metabolic syndrome was defined according to the International Diabetes Federation (IDF). RESULTS: The FTO rs1421085 variant conferred an increased risk to MetS (OR=1.61, 95% CI=1.14-2.26, P=0.024) that was abolished when adjusted for fasting plasma glucose (FPG), suggesting that the association may be due to variation in FPG levels. Indeed, this variant was associated to FPG (OR = 1.7, 95% CI=1.23-2.44, P=0.002) independently from BMI or age. The second polymorphism rs8057044 was associated with high blood pressure levels (OR=1.45, 95% CI=1.06-1.99, P=0.019). CONCLUSIONS: This is the first study highlighting the association between FTO gene variants and MetS in Tunisian population. These findings provide evidence that FTO gene may play a critical role in leading to MetS in Tunisian population.