Metabolic Syndrome: a genomic approach

METABOLIC SYNDROME: A GENOMIC APPROACH Doctoral Student: Antonio Mori The metabolic syndrome (MetS) is a cluster of interrelated metabolic factors (MRCs) such as elevated Triglycerides (ETrig.), reduced HDL-C (RHDL-C), elevated waist circumference (EWC), elevated blood pressure (EBP) and elevated fasting glucose (EFG), that occur together and over time promote the development of cardiovascular disease and type 2 diabetes. Several strong clues support a genetic basis in MetS and MCRs. In the Italian population, little is currently known upon possible predisposing genetic variants associated with MetS and MRCs phenotypes. For this thesis, an exploratory Genome-Wide Association Analysis was performed on 3113 Italian Caucasian individuals of the INCIPE cohort. The MetS diagnosis was evaluated according the 2009 International Diabetes Federation definition. Globally, 37 novel 'genome-significant variants' with Minor Allelic Frequency>1% were detected: 2 MetS-associated, 11 ETrig-associated, 10 RDHL-C-associated, 8 EWC-associated, 6 EBP-associated, and 0 EFG-associated. The variants were located in genomic loci with different functional role. In addition, most of such variants showed pleiotropic signals among MetS and MRCs. In conclusion, these results suggest that a pleiotropic genetic architecture based on a multiple genomic and epigenetic determinants may contribute to etiopathogenesis of MetS or MRCs in the Italian population.