Abstract
Despite the availability of effective antihypertensive drugs, there is a large variation in response to these drugs. This study investigates whether polymorphisms in the angiotensin converting enzyme (I/D), angiotensinogen (M235T), α-adducin (G460W), angiotensin II type 1 receptor (1166A/C), or G protein β3-subunit (825C/T) gene modify the mean difference in blood pressure levels among diuretics, β-blockers, or ACE-inhibitors users. Data were used from the Doetinchem Cohort Study, and blood pressure data were collected from GPs (1987–1997). A marginal generalized linear model (GEE) was used to assess the gene–drug interaction on the mean difference in systolic/diastolic blood pressure. In total, 625 hypertensive individuals were included with a total of 5262 measurements of blood pressure. Only the interaction between diuretic use and the GNB3 825C/T polymorphism was significant (C allele versus TT systolic blood pressure (SBP): 4.33 mmHg [95% CI: 0.14–8.54]). Thus, the mean SBP level among diuretic users may be modified by the GNB3 825C/T polymorphism.
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References
Collins R, MacMahon S . Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease. Br Med Bull 1994; 50: 272–298.
Hansson L, Lindholm LH, Ekbom T, Dahlof B, Lanke J, Schersten B et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity in the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999; 354: 1751–1756.
Schelleman H, Klungel OH, Kromhout D, de Boer A, Stricker BHCh, Verschuren WMM . Prevalence and determinats of undertreatment of hypertension in the Netherlands. J Hum Hypert 2004; 18: 317–324.
Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71: 169–180.
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F . An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343–1346.
Manunta P, Cusi D, Barlassina C, Righetti M, Lanzani C, D’Amico M et al. Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients. Kidney Int 1998; 53: 1471–1478.
Virchow S, Ansorge N, Rubben H, Siffert G, Siffert W . Enhanced fMLP-stimulated chemotaxis in human neutrophils from individuals carrying the G protein beta3 subunit 825 T-allele. FEBS Lett 1998; 436: 155–158.
Schelleman H, Stricker BH, De Boer A, Kroon AA, Verschuren MW, Van Duijn CM et al. Drug–gene interactions between genetic polymorphisms and antihypertensive therapy. Drugs 2004; 64: 1801–1816.
Turner ST, Schwartz GL, Chapman AB, Boerwinkle E . C825T polymorphism of the G protein beta(3)-subunit and antihypertensive response to a thiazide diuretic. Hypertension 2001; 37: 739–743.
Verschuren WMM, Leer van EM, Blokstra A, Seidell JC, Smit HA, Bueno de Mesquita HB et al. Cardiovascular disease risk factors in The Netherlands. Neth J Cardiol 1993; 4: 205–210.
World Health Organization. International Classification of Diseases, 10th Revision (ICD-10). WHO Switzerland, World Health Organization: Geneva, 1992.
Anonymous. Guidelines for ATC Classification and DDD Assignment, 3rd edn. WHO collaberating Centre for drug statistics Methodology: Oslo, 2000.
Beeks E, Janssen RG, Kroon AA, Keulen ET, Geurts JM, de Leeuw PW et al. Association between the alpha-adducin Gly460Trp polymorphism and systolic blood pressure in familial combined hyperlipidemia. Am J Hypertens 2001; 14: 1185–1190.
Russ AP, Maerz W, Ruzicka V, Stein U, Gross W . Rapid detection of the hypertension-associated Met235-->Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993; 2: 609–610.
Siffert W, Rosskopf D, Siffert G, Busch S, Moritz A, Erbel R et al. Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet 1998; 18: 45–48.
Henskens LH, Spiering W, Stoffers HE, Soomers FL, Vlietinck RF, de Leeuw PW et al. Effects of ACE I/D and AT1R-A1166C polymorphisms on blood pressure in a healthy normotensive primary care population: first results of the Hippocates study. J Hypertens 2003; 21: 81–86.
Acknowledgements
This study was financially supported by The Netherlands Heart Foundation, grant number: 2001.064; the Ministry of Health, Welfare and Sport of the Netherlands, and the National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
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Schelleman, H., Stricker, B., Verschuren, W. et al. Interactions between five candidate genes and antihypertensive drug therapy on blood pressure. Pharmacogenomics J 6, 22–26 (2006). https://doi.org/10.1038/sj.tpj.6500339
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DOI: https://doi.org/10.1038/sj.tpj.6500339
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