Clustering of metabolic abnormalities in obese individuals: the role of genetic factors

The objective of this paper is to review the current evidence in support of genetic factors underlying the clustering of components of the metabolic s yndrome in obese individuals. It has become clear that individual features of the metabolic syndrome are partially determined by familial factors some of which are unique to a given component and others that are shared among several features. A few candidate genes, encoding proteins of glucose, insu lin and lipid metabolism, lipolytic cascade, fatty acid intestinal absorpti on, glucocorticoid metabolism, haemostasis acid blood pressure, have been a ssociated with a clustering of metabolic abnormalities, although the functi onal significance of these associations remains to be established. Furtherm ore, genetic polymorphisms, such as those detected at several lipoprotein m etabolism loci, can modulate the relationships between different components of the metabolic syndrome. An overfeeding study conducted on identical twi ns has demonstrated that genetic factors play an important role in the resp onsiveness to changing energy balance conditions. Leptin receptor, beta2 ad renergic receptor and glucocorticoid receptor gene polymorphisms have been associated with an augmented clustering of metabolic abnormalities in respo nse to overfeeding. Gene-gene interaction effects between markers of the al pha 2A, beta2 and beta3 adrenergic receptor genes on components of the meta bolic syndrome have been described. Genetic factors also seem to modify the responsiveness of metabolic syndrome features to endurance training. A gro wing understanding of the genetic architecture of the metabolic syndrome ma y help in the prevention of this condition. The reduction of excess body fa t, the most common clinical feature among the cluster of metabolic abnormal ities, should be the focus of the prevention and treatment of the metabolic syndrome.