Genetic and physiological insights into the metabolic syndrome

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2005-09, Vol.289 (3), p.R663-R669
• Main Authors: Hegele, Robert A, Pollex, Rebecca L
• Format: Article
• Language: English
• Subjects: Canada - epidemiology; Humans; Indians, North American - statistics & numerical data; Inuits - statistics & numerical data; Lamin Type A; Lamins - genetics; Lipodystrophy - genetics; Metabolic Syndrome - epidemiology; Metabolic Syndrome - genetics; Metabolic Syndrome - physiopathology; Mutation; PPAR gamma - genetics; Prevalence
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00275.2005

Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute and University of Western Ontario, London, Ontario, Canada Submitted 15 April 2005 ; accepted in final form 6 May 2005 The metabolic syndrome (MetS) is a common phenotype that is clinically defined by threshold values applied to measures of central obesity, dysglycemia, dyslipidemia, and/or elevated blood pressure, which must be present concurrently in any one of a variety of combinations. Insulin resistance, although not a defining component of the MetS, is nonetheless considered to be a core feature. MetS is important because it is rapidly growing in prevalence and is strongly related to the development of cardiovascular disease. To define etiology, pathogenesis and expression of MetS, we have studied patients, specifically Canadian families and communities. One example is familial partial lipodystrophy (FPLD), a rare monogenic form of insulin resistance caused by mutations in either LMNA , encoding nuclear lamin A/C (subtype FPLD2), or in PPARG , encoding peroxisomal proliferator-activated receptor- (subtype FPLD3). Because it evolves slowly and recapitulates key clinical and biochemical attributes, FPLD seems to be a useful monogenic model of MetS. A second example is the disparate MetS prevalence between two Canadian aboriginal groups that is mirrored by disparate prevalence of diabetes and cardiovascular disease. Careful phenotypic evaluation of such special cases of human MetS by using a wide range of diagnostic methods, an approach called "phenomics," may help uncover early presymptomatic disease biomarkers, which in turn might reveal new pathways and targets for interventions for MetS, diabetes, and atherosclerosis. dyslipidemia; insulin resistance; cardiovascular disease; Canadian aboriginals; genetics Address for reprint requests and other correspondence: R. A. Hegele, 406-100 Perth Drive, London, Ontario, Canada N6A 5K8 (e-mail: hegele{at}robarts.ca )