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OIII‐B‐1
Author(s) -
Gong Y.,
Beitelshees A. L.,
Stauffer L. A.,
Langaee T. Y.,
CooperDeHoff R. M.,
Pepine C. J.,
Johnson J. A.
Publication year - 2006
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.2005.12.110
Subject(s) - atenolol , medicine , haplotype , odds ratio , trandolapril , endocrinology , single nucleotide polymorphism , calcium channel blocker , confounding , pharmacogenetics , pharmacology , ace inhibitor , genotype , blood pressure , biology , genetics , angiotensin converting enzyme , gene
PURPOSE To test the hypothesis that polymorphisms (SNPs) of β1 and β2 adrenergic receptors (ADRB1 & 2) are associated with the number of drugs needed to reach BP control in the β‐blocker arm of INVEST, which enrolled patients with hypertension and coronary artery disease (CAD). METHODS DNA samples were obtained from 3012 patients who received atenolol, with addition of diuretic then ACE inhibitor if needed for BP control or per treatment guideline. Five SNPs were genotyped by Pyrosequencing: ADRB1 S49G, R389G; ADBR2 G16R, Q27E, C523A. Logistic regression was performed to model the number of drugs taken at the time of BP control with genotypes/haplotypes adjusting for age, gender, BMI and other common confounding factors of CAD. RESULTS G389 and the ADRB2 haplotype G16‐E27‐C523 were associated with the need for more drugs to control BP. G389 homozygotes were more likely to require more drugs to control BP than R389 homozygotes (odds ratio 1.31[1.04–1.66]) and heterozygotes (1.35[1.07, 1.70]), as were patients with 2 (vs. 0) copies of ADRB2 haplotype GEC (1.43[1.11–1.85]). Patients with higher baseline systolic BP, BMI > 30, diabetes, history of heart failure were also more likely to need more drugs to control BP than those without these risk factors. CONCLUSIONS These data suggest that ADRB1 G389 and ADRB2 haplotype GEC may affect variable BP response to atenolol therapy in older hypertensives with CAD, thus influencing the number of drugs needed to control BP in a β‐blocker‐based drug regimen. Clinical Pharmacology & Therapeutics (2005) 79 , P30–P30; doi: 10.1016/j.clpt.2005.12.110