Genetic Determinants of the Metabolic Syndrome

The metabolic syndrome is a commonly encountered clinical phenotype presenting as concurrent metabolic abnormalities, including central obesity, dysglycemia, dyslipidemia, and hypertension. Several definitions exist, and it is debated whether or not the clustered risk factors impart a higher cardiovascular risk than the simple sum of the individual components. Nevertheless, the concept of a metabolic syndrome has proven helpful in emphasizing the importance of obesity, insulin resistance and related traits in relation to cardiovascular disease risk. Furthermore, the metabolic syndrome as defined by the National Cholesterol Education Program appears to have a component of heritability, which suggests a genetic basis. Indeed, patients with certain rare single-gene disorders express clusters of abnormalities commonly seen in the metabolic syndrome. Moreover, studies indicate that common genetic variants are associated with the development of this syndrome, although the associations are quite weak and replication of findings has been poor. As with most complex traits, it is premature to propose molecular genetic testing for diagnosis, treatment or both. Unresolved issues include the roles of gene-environment interactions, ethnicity, and sex. In this review, we look at the currently available evidence for common genes that predispose to the development of the metabolic syndrome.