Genetic Susceptibility to the Metabolic Syndrome

There is clear evidence that type 2 diabetes and the Metabolic Syndrome are inherited; therefore much hope has been given to attempts to identify genetic markers which could aid in the diagnosis of these conditions. Success has been limited, but not lacking; probably the worst limitation has been our desire to find a simple explanation for a polygenic multifactorial disease. Several single nucleotide polymorphisms (SNPs) or combinations of them (haplotypes) have been identified in individuals with the Metabolic Syndrome in genes encoding for the β2- and β3-adrenergic receptor, calpain 10, PPARγ, skeletal muscle glycogen synthase (GYS1), adiponectin, etc. However, each of these genes contributes only a small proportion to the individual and population risk of the Metabolic Syndrome and this contribution seems to differ between different parts of the world. The population-attributable risk for type 2 diabetes of the Pro12Ala polymorphism in the PPARγ gene is about 20%, whereas for the calpain 10 haplotype 14% in Mexican Americans but only 4% in Europeans. More importantly, the risk is further influenced by environmental factors like diet ( PPARγ ) or exercise (GYS1) .