Haplotypes of the beta-2 adrenergic receptor associate with high diastolic blood pressure in the Caerphilly prospective study.
OBJECTIVE
Current evidence demonstrates that both genetic and environmental factors influence blood pressure. The sympathetic nervous system is a key player in blood pressure control and functional genetic variants of the beta-2 adrenergic receptor (B2AR) have been identified and implicated in the pathogenesis of hypertension. The present study aimed to determine the effects of common haplotypes of the B2AR gene upon blood pressure in the Caerphilly Prospective Study.


METHODS
Two thousand five hundred and twelve men (aged 45-59 years) participated in the study. We selected individuals in the upper (n = 347) and lower (n = 279) quintiles of the diastolic blood pressure distribution fixed at two time points [phase 2 (1984-88) or phase 3 (1989-93)] as cases and controls.


METHODS
We analysed two functional polymorphisms (Arg16Gly and Gln27Glu) of B2AR and their haplotypes.


RESULTS
We found a higher risk of hypertension in individuals homozygous for the Gln27 compared to those individuals homozygous for Glu27 [odds ratio (OR) = 1.94; 95% confidence interval (CI) = 1.34-2.81; P = 0.001]. Three haplotypes (Gly16Gln27, Gly16Glu27 and Arg16Gln27) were present in both quintile groups. Logistic regression analysis showed that haplotypes with a Gln27 allele (Gly16Gln27 and Arg16Gln27) conferred a significantly higher risk for hypertension than the Gly16Glu27 haplotype (OR = 1.55; 95% CI = 1.11-2.17, OR = 1.37; 95% CI = 1.04-1.81; P = 0.009 and P = 0.027, respectively). However, there was no evidence to support a statistically significant difference in odds ratios for the Gly16Gln27 and Arg16Gln27 haplotypes (P = 0.477), suggesting that it is the Gln27 allele alone, rather than any haplotype, which best explains the association.


CONCLUSIONS
In a prospectively studied Caucasian male cohort, high diastolic blood pressure was associated with B2AR haplotypes containing the pro-downregulatory Gln27 variant.
Binder
Alexander
A
Krankenhaus Barmherzige Brüder, Teaching Hospital Medical University Graz, Austria.
Garcia
Edwin
E
Wallace
Chris
C
Gbenga
Kazeem
K
Ben-Shlomo
Yoav
Y
Yarnell
John
J
Brown
Philippa
P
Caulfield
Mark
M
Skrabal
Falko
F
Kotanko
Peter
P
Munroe
Patricia
P
D001794:Blood Pressure / Q000235:genetics*; D003971:Diastole; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012044:Regression Analysis; D044465:White People
D018343:Receptors, Adrenergic, beta-2