Association of rs9939609 Polymorphism with Metabolic Parameters and FTO Risk Haplotype Among Tunisian Metabolic Syndrome

International audienceBackground: Variants in the fat mass and obesity-associated (FTO) gene are associated with obesity and type 2 diabetes mellitus.Aim of the study: This study aims to assess the association of the rs9939609 variant and haplotypes in FTO gene with metabolic syndrome (MetS) components in a Tunisian population sample.Methods: A total of 685 Tunisian subjects were genotyped for the rs9939609T>A using TaqMan allelic discrimination assay. Two variants rs1421085T>C and rs8057044A>G already genotyped in a previous study were used to test haplotype association of the FTO gene.Results: Genotype distribution of the variant rs9939609 was different between MetS and controls (P = 0.017). Individuals carrying TA genotypes had a significantly increased risk independently of body mass index or age (P = 0.009). The variant rs9939609 was also associated with impaired fasting glucose (IFG) (P = 0.002). Among the eight haplotypes in the population, the haplotype GCA was significantly associated with a higher risk of developing the MetS, higher systolic blood pressure, and higher levels of fasting glucose and triglycerides (TGs) in the total sample and females, separately. Separate analysis by gender revealed a protective haplotype TGT among women (P = 0.023).Conclusions:FTO haplotypes have a strong influence on blood pressures and TG and IFG levels. These findings provide evidence that FTO gene may play a critical role in leading to MetS in Tunisian population

Genetic characterization of suspected MODY patients in Tunisia by targeted next-generation sequencing

International audienceAIMS: Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance pattern. The diagnosis of MODY and its subtypes is based on genetic testing. Our aim was investigating MODY by means of next-generation sequencing in the Tunisian population.METHODS: We performed a targeted sequencing of 27 genes known to cause monogenic diabetes in 11 phenotypically suspected Tunisian patients. We retained genetic variants passing filters of frequency in public databases as well as their probable effects on protein structures and functions evaluated by bioinformatics prediction tools.RESULTS: Five heterozygous variants were found in four patients. They include two mutations in HNF1A and GCK that are the causative genes of the two most prevalent MODY subtypes described in the literature. Other possible mutations, including novel frameshift and splice-site variants were identified in ABCC8 gene.CONCLUSIONS: Our study is the first to investigate the clinical application of targeted next-generation sequencing for the diagnosis of MODY in Africa. The combination of this approach with a filtering/prioritization strategy made a step towards the identification of MODY mutations in the Tunisian population