Genetic forms of the cardiometabolic syndrome: what can they tell the clinician?
A well-worn medical aphorism states that "when you hear hoof beats, think of a horse and not a zebra." When applying this principle to the cardiometabolic syndrome (CMS), the horse would be represented by the prevalent CMS phenotype that affects approximately 30% of individuals in Westernized societies, while the zebra is represented by very rare conditions--such as lipodystrophy syndromes--that share some features with the more prevalent CMS. For instance, familial partial lipodystrophy types 2 and 3 result from heterozygous mutations in LMNA, encoding nuclear lamin A/C, and in PPARG, encoding peroxisome proliferator-activated receptor (PPAR)-gamma, respectively. Patients with either subtype of partial lipodystrophy exhibit an increased ratio of central to peripheral fat stores, dysglycemia, dyslipidemia, and hypertension, with predisposition for developing insulin-resistant diabetes and atherosclerosis end points. Sometimes, however, the zebra serves as a model that can help us understand the horse, so that the rare partial lipodystrophies might offer some insight into pathogenesis and treatment of the more prevalent CMS.
Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5K8.
George
G
Yuan
Robert A
RA
Hegele
D006801:Humans; D008060:Lipodystrophy / Q000235:genetics; D052496:Lipodystrophy, Familial Partial / Q000235:genetics / Q000628:therapy; D024821:Metabolic Syndrome / Q000235:genetics*; D009765:Obesity / Q000150:complications