Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years.
BACKGROUND
The genes responsible for obesity are candidate genes for obesity-related diseases, such as hypertension. Functional polymorphisms in the beta2- and beta3-adrenergic receptors have been reported to be associated with hypertension and obesity.


RESULTS
To longitudinally clarify the relevance to alterations in beta-adrenergic receptor polymorphisms related to weight gain, blood pressure (BP) elevation, and sympathetic nerve activity as measured by plasma norepinephrine level, we studied 160 young, nonobese, normotensive men. Changes in body weight, BP, plasma norepinephrine levels, and beta2-adrenergic (Arg16Gly, Gln27Glu) and beta3-adrenergic (Trp64Arg) receptor polymorphisms were measured periodically over a 5-year period. Weight gain and BP elevation were defined as > or =10% increases from entry levels over 5 years in body mass index or mean BP. The presence of the Gly16 allele of Arg16Gly was associated with a higher frequency of weight gain and BP elevation over the 5-year period. The subjects carrying the Glu27 allele of Gln27Glu and the Trp64 allele of Trp64Arg had a higher frequency of BP elevation. Significantly higher levels of plasma norepinephrine at entry and at year 5 were observed in the subjects with the Gly16 allele of Arg16Gly and the Glu27 allele of Gln27Glu compared with those without the Gly16 or the Glu27 alleles.


CONCLUSIONS
These results demonstrate that the Gly16 allele is related to greater weight gain and BP elevation. Additionally, Glu27 and Trp64 alleles are linked to BP elevation. The subjects carrying the beta2-polymorphisms linked to weight gain and BP elevation also have higher plasma norepinephrine levels that are present at entry before weight gain and BP elevation. These findings suggest that beta2-adrenergic receptor polymorphisms in association with a heightened sympathetic nerve activity could predict the future onset of obesity and hypertension, as shown in the 5-year longitudinal study.
Masuo
Kazuko
K
Human Neurotransmitter Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia. kmasuo@baker.edu.au
Katsuya
Tomohiro
T
Fu
Yuxiao
Y
Rakugi
Hiromi
H
Ogihara
Toshio
T
Tuck
Michael L
ML
D000328:Adult; D001794:Blood Pressure / Q000235:genetics; D001837:Body Weights and Measures; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000235:genetics; D011110:Polymorphism, Genetic / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D013564:Sympathetic Nervous System; D015430:Weight Gain / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D009638:Norepinephrine