Abstract
Life-style-related disease such as obesity and type 2 diabetes mellitus are heterogeneous and overlapping disorders, both having strong genetic components. Visceral fat obesity is a particularly strong risk factor for insulin resistance, hypertension, and dyslipidemia. The β3-adrenergic receptor (β3-AR) is a seven-membrane-spanning receptor expressed in brown and white adipose tissues, and it is thought to regulate thermogenesis and lipolysis. A polymorphism (Trp64Arg) in the β3-AR gene at the junction between the first transmembrane domain and the first intracellular loop is prevalent in diverse populations including Pima Indians and Japanese. A Trp64Arg polymorphism in the β3-AR is associated with obesity, several features of hyperinsulinemia/insulin resistance, and increased blood pressure, as well as decreased metabolic rate and earlier onset of type 2 diabetes mellitus. The current consensus is that the Trp64Arg polymorphism is a modest contributor to obesity and obesity-related traits (a “thrifty genotype”) and that ethnic background and possibly gender are important determinants of phenotypic expression. Furthermore, obese Japanese women with the Trp64Arg polymorphism are more resistant to weight-loss treatment, suggesting that this polymorphism is clinically relevant. An update and critical review of obesity-related SNPs and treatment of obesity are also discussed.
