Haplotypes of the adrenergic system predict the blood pressure response to beta-blockers in women with essential hypertension.
OBJECTIVE
To analyze the association of haplotypes of the adrenergic system with essential hypertension and with the blood pressure response to beta-blockers.


METHODS
In 1112 never-treated essential hypertension patients and 203 normotensive controls, tightly linked SNPs of beta-adrenergic receptors (ADRB1 - Ser49Gly and Arg389Gly; ADRB2 - Cys19Arg, Gly16Arg and Gln27Glu) and the G-protein beta3-subunit (GNB3 - A3882C, G5249A and C825T) were genotyped. Association of haplotypes with essential hypertension and with the blood pressure response to atenolol 50 mg twice daily in a subgroup of essential hypertension patients (n = 340) was evaluated (Haploview 3.2).


RESULTS
No SNPs or haplotypes were associated with essential hypertension. In females only, GNB3 SNPs and haplotypes were associated with the blood pressure response (p < 0.05).


CONCLUSIONS
Our study confirmed the sex-specific association of GNB3 with the blood pressure response to atenolol with no substantial advantage of the analysis of haplotypes over SNPs.
Chair of Emergency, University of Sassari Medical School and Hypertension & Cardiovascular Prevention Center, Viale S Pietro 8, 07100 Sassari, Italy. ffiligheddu@uniss.it
Fabiana
F
Filigheddu
Giuseppe
G
Argiolas
Simona
S
Degortes
Roberta
R
Zaninello
Francesca
F
Frau
Silvia
S
Pitzoi
Emanuela
E
Bulla
Patrizia
P
Bulla
Chiara
C
Troffa
Nicola
N
Glorioso
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001262:Atenolol / Q000494:pharmacology; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
C547787:ADRB1 protein, human; D000319:Adrenergic beta-Antagonists; D017931:DNA Primers; C454420:G-protein beta3 subunit; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D001262:Atenolol; D020962:Heterotrimeric GTP-Binding Proteins