Polymorphisms of the beta2 -adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies.
OBJECTIVE
The beta2-adrenoceptor (ADRB2) plays a pivotal role in signalling in relation to hypertension and obesity. Polymorphisms of the ADRB2 gene have been shown to be potentially related to essential hypertension and other non-cardiovascular disease phenotypes. We investigated whether genetic variation of the ADRB2 gene might be related to essential hypertension or myocardial infarction (MI).


METHODS
Four ADRB2 gene polymorphisms C19R (T-47C), T-20C, G16R (G+46A), Q27E (C+79G) were investigated in two studies: PEGASE, a study of moderate to severe hypertension (707 cases) conducted in France, and ECTIM, a case-control study of MI (1178 cases, 1187 controls) conducted in France, Northern Ireland and Scotland. Genotyping was performed using allele-specific oligonucleotides.


RESULTS
The ADRB2 polymorphisms T-20C and Q27E were found to be completely concordant, generating the haplotypes [T-20-Q27] and [C-20-E27]. Three main haplotypes accounted for 94% of all haplotypes: [R19-G16-E27] (39%), [C19-R16-Q27] (35%) and [C19-G16-Q27] (20%). Haplotype frequencies were not significantly different between countries. Allele and genotype frequencies did not differ significantly between cases with essential hypertension or MI and control subjects. There was no association of the polymorphisms with early onset hypertension, blood pressure level, coronary artery stenosis or any other phenotype measured in these study populations. In the ECTIM Study, our calculation revealed that we could have detected an odds ratio (OR) for MI of 1.3 with 80% power at a 5% type I error probability, the corresponding value for the PEGASE Study being an OR of 1.6 for hypertension.


CONCLUSIONS
From our present analysis we conclude that the ADRB2 gene polymorphisms studied do not contribute in any important way to the risk of essential hypertension or MI in subjects of European ancestry.
Herrmann
Stefan-Martin
SM
Institut National de la Santé et de la Recherche Médicale (Inserm) SC7/U525, Paris, France. hermann@medizin.fu-berlin.de
Nicaud
Viviane
V
Tiret
Laurence
L
Evans
Alun
A
Kee
Frank
F
Ruidavets
Jean-Bernard
JB
Arveiler
Dominique
D
Luc
Gerald
G
Morrison
Caroline
C
Hoehe
Margret R
MR
Paul
Martin
M
Cambien
François
F
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005602:France / Q000453:epidemiology; D017353:Gene Deletion; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012737:Sex Factors; D006113:United Kingdom / Q000453:epidemiology; D014944:World Health Organization
D018343:Receptors, Adrenergic, beta-2