beta2- and beta3-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 beta2- and beta3-adrenoceptor polymorphisms are associated with obesity and hypertension. In the present study, we examine the relationships of beta2- and beta3-adrenoceptor polymorphisms with further weight gain-induced BP elevation in obese subjects. Changes in BP, body weight, total body fat-mass, waist-to-hip ratio, plasma norepinephrine (NE) and leptin levels, and beta2(Arg16Gly)- and beta3(Trp64Arg)-adrenoceptor polymorphisms were measured periodically over a 5-year period in 55 entry obese (body mass index [BMI]> or =25.0 kg/m(2)) normotensive (BP<140/90 mmHg) men. BP elevation and weight gain were defined as > or =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 Arg16GIy 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 beta3-adrenoceptor polymorphisms relates to weight gain-induced BP elevation accompanying high plasma NE (heightened sympathetic activity) in obese men. The Gly16 allele of the beta2-adrenoceptor polymorphisms links to weight gain-induced BP elevation associated with leptin resistance. beta2- and beta3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects.
Kawaguchi
Hideki
H
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Masuo
Kazuko
K
Katsuya
Tomohiro
T
Sugimoto
Ken
K
Rakugi
Hiromi
H
Ogihara
Toshio
T
Tuck
Michael L
ML
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D015331:Cohort Studies; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D020738:Leptin / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000150:complications*; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D015430:Weight Gain / Q000235:genetics
D020738:Leptin; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D009638:Norepinephrine