Premium
Beta 2‐adrenergic receptor (B2AR) polymorphisms and antihypertensive response to beta‐blocker therapy in the invest trial
Author(s) -
Gong Y.,
Beitelshees A.L.,
Stauffer L.,
Gaston K.,
Sloan A.,
Yarandi H.N.,
Langaee T.Y.,
DeHoff R.M.,
Pepine C.J.,
Johnson J.A.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.086
Subject(s) - atenolol , blood pressure , medicine , single nucleotide polymorphism , essential hypertension , diastole , pharmacology , beta blocker , pharmacogenetics , endocrinology , cardiology , genotype , genetics , biology , gene , heart failure
Purpose Polymorphisms (SNPs) of the B2AR gene have been associated with hypertension. We investigated the association of several B2AR SNPs and blood pressure (BP) responses to atenolol. Methods Data and genomic samples were obtained from 740 participants of the International Verapamil‐Trandolapril Study (INVEST) trial with hypertension and coronary artery disease in whom atenolol was added as monotherapy or was added to stable background therapy. Arg16Gly, Gln27Glu and a synonymous C→A SNP at nt523 were genotyped by pyrosequencing. Analysis of covariance was used to compare BP responses to atenolol at 6 weeks among genotypes adjusting for age (66.2± 9.2), BMI, baseline BP and race. Results Minor allele frequencies for Arg16Gly, Gln27Glu and nt523 C to A were 0.42, 0.34 and 0.28, respectively. Codon 16 polymorphisms were not associated with BP response to atenolol. 27Gln and nt523A alleles of B2AR were associated with significantly better systolic blood pressure (SBP) response to atenolol (p= 0.0080 and p= 0.0288). 27Gln carriers also showed better diastolic blood pressure (DBP) response (p= 0.0242) to atenolol therapy. (see Table) Conclusion Our data suggest that codon 27 and nt523 gene variants may be important determinants of variable BP response to atenolol therapy in older hypertensives with coronary disease. Clinical Pharmacology & Therapeutics (2005) 77 , P22–P22; doi: 10.1016/j.clpt.2004.11.086Gln27Glu C523ASBP DBP SBPGln/Gln (n = 319) 137.09 ± 17.29 * 79.23 ± 9.52 ** C/C (n = 370) 140.42 ± 18.14 Gln/Glu (n = 315) 140.28 ± 18.66 80.53 ± 9.93 C/A (n = 287) 138.93 ± 18.07 Glu/Glu (n = 86) 142.83 ± 17.71 82.11 ± 9.65 A/A (n = 60) 133.51 ± 17.24 ***adjusted means± SD; * p= 0.01 vs. Glu/Glu ** p= 0.012 vs. Glu/Glu *** p= 0.008 vs. C/C