Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR and PEAR-2))

The primary aim of the Pharmacogenomic Evaluation of Antihypertensive Responses grant (funded by NIH Pharmacogenomic Research Network grant U01 GM074492) was to identify genetic determinants of blood pressure response and adverse events after antihypertensive treatments. Two different clinical trials with genomic information available were included: PEAR-1 and PEAR-2 studies. The PEAR-1 study (clinicaltrials.gov identifier NCT00246519) was a randomized controlled clinical trial evaluating genetic determinants of BP responses and adverse metabolic responses to atenolol and hydrochlorothiazide (HCTZ) monotherapy and in combination (PMID: 19249413). Briefly, PEAR-1 recruited 768 hypertension individuals with uncomplicated hypertension who were randomized to either monotherapy of atenolol 50 mg daily or HCTZ 12.5 mg daily for 3 weeks, followed by dose titration to 100 mg and 25 mg daily, then the combination therapy. BP and metabolic responses to monotherapy and combination therapy were assessed after an average of 9 weeks of antihypertensive treatment. BP was measured using three different methods: home, office and ambulatory. For the BP analysis, a composite weighted average of the office, home, ambulatory daytime and nighttime BP responses was calculated based on the row sums of the inverse of the inter-method covariance matrices. Genomic DNA from PEAR-1 participants was genotyped using the Illumina Human Omni1MQuad BeadChip (Illumina, San Diego, CA, USA). The PEAR-2 study was a multicenter sequential monotherapy clinical trial (clinicaltrials.gov identifier NCT01203852) evaluating genetic determinants of BP response to metoprolol monotherapy and chlorthalidone monotherapy. After a washout period (if necessary), eligible hypertensive patients with uncomplicated hypertension received metoprolol tartrate 50 mg twice daily for 3 weeks and the dose was increased to 100 mg twice daily for an additional six weeks if an inadequate response was observed (>120/70 mm Hg and heart rate >55 beats/min). After second washout period, patients received chlorthalidone monotherapy. Home and office BP measurements were collected in PEAR-2 study. We have previously demonstrated that home BP is the more informative single BP measurement compared to the office BP measurement. Therefore, home BP is the phenotype used for the genome-wide association analysis for PEAR-2. PEAR-2 samples were genotyped using the Illumina Human Omni2.5S Beadchip (Illumina, San Diego, CA, USA).]]>
we conducted genome-wide association meta-analyses of ≈1.1 million single-nucleotide polymorphisms in African Americans with primary hypertension treated with atenolol from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=150). The patients were genotyped on Illumina 1MQuad Beadchip and imputed to Hapmap III. The analysis was performed in ProbAble software and covariates included age, gender, baseline diastolic blood pressure and the first 2 principle components.we conducted genome-wide association meta-analyses of ≈1.1 million single-nucleotide polymorphisms in African Americans with primary hypertension treated with atenolol from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=150). The patients were genotyped on Illumina 1MQuad Beadchip and imputed to Hapmap III. The analysis was performed in ProbAble software and covariates included age, gender, baseline systolic blood pressure and the first 2 principle components.we conducted genome-wide association meta-analyses of ≈1.1 million single-nucleotide polymorphisms in European Americans with primary hypertension treated with atenolol from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=233). The patients were genotyped on Illumina 1MQuad Beadchip and imputed to Hapmap III. The analysis was performed in ProbAble software and covariates included age, gender, baseline diastolic blood pressure and the first 2 principle components.we conducted genome-wide association meta-analyses of ≈1.1 million single-nucleotide polymorphisms in European Americans with primary hypertension treated with atenolol from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=233). The patients were genotyped on Illumina 1MQuad Beadchip and imputed to Hapmap III. The analysis was performed in ProbAble software and covariates included age, gender, baseline diastolic blood pressure and the first 2 principle components.we conducted genome-wide association meta-analyses of ≈1.1 million single-nucleotide polymorphisms in African Americans with primary hypertension treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=148). The patients were genotyped on Illumina 1MQuad Beadchip and imputed to Hapmap III. The analysis was performed in ProbAble software and covariates included age, gender, baseline diastolic blood pressure and the first 2 principle components.we conducted genome-wide association meta-analyses of ≈1.1 million single-nucleotide polymorphisms in African Americans with primary hypertension treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=148). The patients were genotyped on Illumina 1MQuad Beadchip and imputed to Hapmap III. The analysis was performed in ProbAble software and covariates included age, gender, baseline systolic blood pressure and the first 2 principle components.The data are in the public ftp site.
]]>The data are in the public ftp site.
]]>The data are in the public ftp site.
]]>PEAR 1 and PEAR 2 inclusion criteria were published previously (PMID: 19249413, 24637943). Briefly, males or females, aged between 17 and 65 years old, of any race or ethnicity, with mild to moderate newly diagnosed, untreated, or known uncomplicated hypertension. Study participants were excluded if they had any of the following exclusion criteria: secondary forms of hypertension, treated office SBP >170 mm Hg, isolated systolic hypertension, other diseases requiring treatment with BP-lowering medications, known cardiovascular diseases, diabetes mellitus, primary renal disease, renal insufficiency (serum creatinine > 1.5 mg/dl in men or 1.4 mg/dl in women), liver abnormalities (liver enzymes > 2.5 times the upper limits of normal), pregnancy or lactation, or chronic use of medications that could potentially affect the BP. In addition, the exclusion criteria specific for β-1-blocker therapy were heart rate < 55 beats/min (in the absence of a β-1-blocker), presence of a cardiac pacemaker, history of Raynaud's phenomenon, and asthma or chronic obstructive pulmonary disease.]]>
Study Start Date: PEAR-1: Month, 2005; PEAR-2: Month, 2010 Study Completion Date: PEAR-1: Month, 2010; PEAR-2: Month 2015]]>