Predictors of Antihypertensive Drug Responses: Initial Data from a Placebo-Controlled, Randomized, Cross-Over Study With Four Antihypertensive Drugs (The GENRES Study)

Hiltunen, Timo P.; Suonsyrjä, Timo; Hannila‐Handelberg, Tuula; Paavonen, Kristian; Miettinen, Helena E.; Strandberg, Timo; Tikkanen, Ilkka; Tilvis, Reijo S.; Pentikäinen, Pertti J.; Virolainen, Juha; Kontula, Kimmo

doi:10.1016/j.amjhyper.2006.09.006

Cited by 70 publications

(72 citation statements)

References 27 publications

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“…PTPRD encodes protein-tyrosine phosphatase delta, a signaling molecule that regulates cell growth and differentiation. The significance of rs12346562 was replicated in a cohort of Finnish men from the genetics of drug responsiveness in essential hypertension study (GENRES) 87 . Three other independent groups of hypertensive individuals were examined as part of the replication and validation process.…”

Section: Plausible Variants Uncovered In Unbiased Analysesmentioning

confidence: 94%

A Physiologic Approach to the Pharmacogenomics of Hypertension

Eadon

Chapman

2016

Advances in Chronic Kidney Disease

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Section: Plausible Variants Uncovered In Unbiased Analysesmentioning

confidence: 94%

A Physiologic Approach to the Pharmacogenomics of Hypertension

Eadon

Chapman

2016

Advances in Chronic Kidney Disease

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“…The design of the GENRES study has been described in detail. 13 Briefly, 313 moderately hypertensive Finnish men, aged 35-60 years, were studied. The inclusion criteria were DBP X95 mm Hg in repeated measurements or use of antihypertensive medication.…”

Section: Methods Subjectsmentioning

confidence: 99%

“…As a platform, we used our unique GENRES study (a study on molecular GENetics of drug RESponsiveness in essential hypertension), which compares the antihypertensive effects of four different drug monotherapies in hypertensive men by using a double-blind crossover design. 13 …”

Section: Introductionmentioning

confidence: 99%

STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men

et al. 2011

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Large-scale genome-wide association studies (GWASs) have identified significant associations of common genetic variants with blood pressure (BP) levels. To obtain more evidence for the role of these variants in BP regulation, we studied their association with BP responses to four different antihypertensive drug monotherapies. We selected 19 single-nucleotide variants based on data from five GWASs. The study group consisted of more than 200 hypertensive Finnish men from the GENRES study. Ambulatory BP responses to 4-week treatments with losartan, bisoprolol, hydrochlorothiazide and amlodipine were the primary targets of the study. Secondarily, baseline indicators of the activity of the renin-angiotensin-aldosterone system were studied. After correction for multiple comparisons, the variant rs6749447 in the STK39 gene was significantly associated with BP responses. Thus, the minor rs6749447 allele was associated with a lower systolic and diastolic BP response to losartan (P¼0.0005 and 0.0002, respectively). rs6749447 minor allele homozygotes had marginally higher serum aldosterone/plasma renin activity (PRA) ratios (P¼0.04) than those without this allele. In a replication study on aldosterone and renin levels, another cohort of hypertensive patients (n¼311) showed a similar trend. When the two cohorts were combined, the aldosterone level (P¼0.02) and the aldosterone/PRA ratio (P¼0.01) were higher in subjects homozygous for the minor rs6749447 allele than in other subjects. The present study shows that pharmacogenetic approaches may provide evidence that complements systematic genome-wide strategies by identifying gene loci that not only affect the BP level but also might modify its response to pharmacologic interventions.

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“…30 Readings were taken four times an hour during the daytime and twice an hour during the night. Single observations were excluded from the analyses because of low pulse pressure (below 15 mm Hg for systolic blood pressures lower than 120 mm Hg; below 20 mm Hg for systolic pressures higher than 120 mm Hg), high heart rates (X110), standing up or being awake during night times, or lying down during daytime.…”

Section: -H Ambulatory Blood Pressure Measurementmentioning

confidence: 99%

“…In addition, intensive physical exercise was not allowed during the recordings. 30 The recordings were analyzed in a fully blinded fashion. In the analysis, daytime was defined as hours 0600 to 2200 h, and night time as hours 2200 to 0600 h.…”

Section: -H Ambulatory Blood Pressure Measurementmentioning

confidence: 99%

Effects of long-term intake of lactotripeptides on cardiovascular risk factors in hypertensive subjects

Jauhiainen

Niittynen²,

Orešič

et al. 2012

Eur J Clin Nutr

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BACKGROUND/OBJECTIVES: Lactobacillus helveticus LBK-16H-fermented milk products containing tripeptides isoleucine-prolineproline and valine-proline-proline lower blood pressure in hypertensive subjects using office and home blood pressure registration. The present study was aimed to evaluate the effects of two doses of these lactotripeptides on 24-h ambulatory blood pressure and lipidomics profiles in mildly hypertensive subjects. SUBJECTS/METHODS: In a randomized, double-blind, placebo-controlled parallel group study, 89 mildly hypertensive subjects ingested, after a 1-month run-in period, a fermented milk drink with 5 mg per day of lactotripeptides during 3 months, and a milk drink with 50 mg per day of lactotripeptides for the following 3 months, or a placebo milk drink without lactotripeptides. Ambulatory blood pressure (24 h) was recorded at baseline and at the end of the intervention periods. Lipidomics profiles were characterized before and after the 6-month intervention. RESULTS: After the second intervention period (50 mg per day of lactotripeptides), systolic and diastolic 24-h blood pressures decreased significantly in the peptide, but not in the placebo group. However, the treatment effects À 2.6 mm Hg (95% confidence interval (CI): À 5.7 to 0.4) in systolic and À 1.3 mm Hg (95% CI: À 3.4 to 0.8) in diastolic blood pressure did not reach statistic significance. Ingestion of 5 mg per day of lactotripeptides for 3 months did not lower blood pressure. The peptide group was dominated by decrease in multiple phospholipids (PL). CONCLUSIONS: Ingestion of fermented milk with daily dose of 50 mg of lactotripeptides appears to lower elevated blood pressure slightly from the baseline, but not significantly compared with the placebo group and to induce significant decreases in multiple PL.

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Predictors of Antihypertensive Drug Responses: Initial Data from a Placebo-Controlled, Randomized, Cross-Over Study With Four Antihypertensive Drugs (The GENRES Study)

Abstract: Baseline clinical and BP parameters may be used to predict the efficacy of antihypertensive therapies. The GENRES Study material should provide an excellent platform for future pharmacogenetic analyses of antihypertensive drug responsiveness.

Cited by 70 publications

References 27 publications

A Physiologic Approach to the Pharmacogenomics of Hypertension

A Physiologic Approach to the Pharmacogenomics of Hypertension

STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men

Effects of long-term intake of lactotripeptides on cardiovascular risk factors in hypertensive subjects

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