β2- and β3-adrenoceptor polymorphisms relate to subsequent weight gain and blood pressure elevation in obese normotensive individuals

High blood pressure (BP) is a major determinant of cardiovascular events in obesity. The beta 2- and beta 3-adrenoceptor polymorphisms are associated with obesity and hypertension. In the present study, we examine the relationships of beta 2- and beta 3-adrenoceptor polymorphisms with further weight gain-induced BP elevation in obese subjects. Changes in BID, body weight, total body fat-mass, waist-to-hip ratio, plasma norepinephrine (NE) and leptin levels, and beta 2(Arg16Gly)- and beta 3(Trp64Arg)-adrenoceptor polymorphisms were measured periodically over a 5-year period in 55 entry obese (body mass index [BMI] >= 25.0 kg/m(2)) normotensive (BP<140/90 mmHg) men. BP elevation and weight gain were defined as >= 10% increases from entry levels over 5 years in mean BP or BMI. Obese subjects with weight gain, BP elevation or weight gain-induced BP elevation had higher frequencies of the Gly16 allele of Arg16Gly and Arg64 allele of Trp64Arg. Subjects carrying the Gly16 or Arg64 alleles had significantly greater total fat-mass and waist-to-hip ratio at entry and over a 5-year period compared to the subjects who did not carry these polymorphisms. Subjects carrying the Gly16 allele had similar levels of plasma NE, higher levels of plasma leptin and a lower slope of the regression lines between plasma leptin and NE levels. Those carrying the Arg64 allele had higher plasma NE levels at entry and over a 5-year period compared to the subjects without the Arg64 allele, but plasma leptin levels and slopes were similar. The findings demonstrate that the Arg64 allele of the beta 3-adrenoceptor polymorphisms relates to weight gain-induced BP elevation accompanying high plasma NE (heightened sympathetic activity) in obese men. The Gly16 allele of the beta 2-adrenoceptor polymorphisms links to weight gain-induced BP elevation associated with leptin resistance. beta 2- and beta 3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects.