A Study on Molecular Genetics of Drug Responsiveness in Essential Hypertension

Summary

Blood pressure variation and the risk of essential hypertension have an important genetic component. In most cases susceptibility to essential hypertension is likely determined by the action of more than one gene. The identification of genes causing susceptibility to hypertension is important, since it would give new tools for the diagnosis and enable better etiological classification and specific treatment of the disease. The innovation of this study is to use the response to antihypertensive therapy as an intermediate phenotype. In the study, each subject uses one of four antihypertensive drugs, each as a monotherapy in a rotational fashion, for 28 days in a randomized order. The antihypertensive drugs to be tested include a thiazide diuretic, a beta-adrenergic antagonist, an angiotensin-II receptor antagonist and a calcium channel blocker. The drugs that are selected for the study are "typical" representatives of their groups and long-acting, and the dosages are sufficient but well tolerable.

Timeline

Start

1999-11-25

Primary completion

2004-04-01

Completion

2004-04-01

Publications

• Results Hiltunen TP, Suonsyrja T, Hannila-Handelberg T, Paavonen KJ, Miettinen HE, Strandberg T, Tikkanen I, Tilvis R, Pentikainen PJ, Virolainen J, Kontula K. Predictors of antihypertensive drug responses: initial data from a placebo-controlled, randomized, cross-over study with four antihypertensive drugs (The GENRES Study). Am J Hypertens. 2007 Mar;20(3):311-8. doi: 10.1016/j.amjhyper.2006.09.006.
• Results Suonsyrja T, Hannila-Handelberg T, Paavonen KJ, Miettinen HE, Donner K, Strandberg T, Tikkanen I, Tilvis R, Pentikainen PJ, Kontula K, Hiltunen TP. Laboratory tests as predictors of the antihypertensive effects of amlodipine, bisoprolol, hydrochlorothiazide and losartan in men: results from the randomized, double-blind, crossover GENRES Study. J Hypertens. 2008 Jun;26(6):1250-6. doi: 10.1097/HJH.0b013e3282fcc37f.
• Results Hiltunen TP, Donner KM, Sarin AP, Saarela J, Ripatti S, Chapman AB, Gums JG, Gong Y, Cooper-DeHoff RM, Frau F, Glorioso V, Zaninello R, Salvi E, Glorioso N, Boerwinkle E, Turner ST, Johnson JA, Kontula KK. Pharmacogenomics of hypertension: a genome-wide, placebo-controlled cross-over study, using four classes of antihypertensive drugs. J Am Heart Assoc. 2015 Jan 26;4(1):e001521. doi: 10.1161/JAHA.115.001778.
• Nuotio ML, Sanez Tahtisalo H, Lahtinen A, Donner K, Fyhrquist F, Perola M, Kontula KK, Hiltunen TP. Pharmacoepigenetics of hypertension: genome-wide methylation analysis of responsiveness to four classes of antihypertensive drugs using a double-blind crossover study design. Epigenetics. 2022 Nov;17(11):1432-1445. doi: 10.1080/15592294.2022.2038418. Epub 2022 Feb 25.
• Ala-Mutka EM, Rimpela JM, Fyhrquist F, Kontula KK, Hiltunen TP. Effect of hydrochlorothiazide on serum uric acid concentration: a genome-wide association study. Pharmacogenomics. 2018 Apr;19(6):517-527. doi: 10.2217/pgs-2017-0184. Epub 2018 Mar 27.

Drugs

Indications