Endothelial Nitric Oxide Synthase Haplotypes Are Associated with Features of Metabolic Syndrome (Endocrinology and Metabolism) (Survey‪)‬

The metabolic syndrome, a cluster of disturbed glucose and insulin metabolism, abdominal obesity, dyslipidemia, and hypertension, predicts the development of type 2 diabetes mellitus and cardiovascular disease (1, 2). In addition to lifestyle features such as poor diet and physical inactivity, several studies have suggested a heritable basis to the etiology of metabolic syndrome (3-6). Although this concept has recently been challenged, we and others feel that the heritability of metabolic syndrome represents a powerful valid working hypothesis that unifies the metabolic factors underlying the development of both atherosclerotic cardiovascular disease and diabetes (7, 8). Endothelial nitric oxide synthase (eNOS)2 is involved in production of nitric oxide (NO), a ubiquitous molecule responsible for the maintenance of normal endothelial function. Among its many roles, NO facilitates the uptake and metabolism of glucose in skeletal muscle (9,10). By contrast, the superoxidative effects of NO, which may occur through functional variation in NO synthase genes, may play a role in insulin resistance and type 2 diabetes (11).