A genetic variant in the catechol-O-methyl transferase (COMT) gene is related to age-dependent differences in the therapeutic effect of calcium-channel blockers.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_8422CED755D8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A genetic variant in the catechol-O-methyl transferase (COMT) gene is related to age-dependent differences in the therapeutic effect of calcium-channel blockers.
Périodique
Medicine
Auteur(s)
Xu J., Boström A.E., Saeed M., Dubey R.K., Waeber G., Vollenweider P., Marques-Vidal P., Mwinyi J., Schiöth H.B.
ISSN
1536-5964 (Electronic)
ISSN-L
0025-7974
Statut éditorial
Publié
Date de publication
07/2017
Peer-reviewed
Oui
Volume
96
Numéro
30
Pages
e7029
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Hypertension is the leading risk factor for cardiovascular disease and one of the major health concerns worldwide. Genetic factors impact both the risk for hypertension and the therapeutic effect of antihypertensive drugs. Sex- and age-specific variances in the prevalence of hypertension are partly induced by estrogen. We investigated 6 single nucleotide polymorphisms in genes encoding enzymes involved in estrogen metabolism in relation to sex- and age-specific differences in the systolic and diastolic blood pressure (SBP and DBP) outcome under the treatment of diuretics, calcium-channel blockers (CCBs), angiotensin-converting-enzyme inhibitors, and angiotensin-receptor blockers (ARBs).We included 5064 subjects (age: 40-82) from the population-based CoLaus cohort. Participants were genotyped for the catechol-O-methyltransferase gene (COMT) variants rs4680, rs737865, and rs165599; the uridine-diphospho-glucuronosyltransferase 1A gene family (UGT1A) variants rs2070959 and rs887829; and the aromatase gene (CYP19A1) variant rs10046. Binomial and linear regression analyses were performed correcting for age, sex, body mass index, smoking, diabetes, and antihypertensive therapy to test whether the variants in focus are significantly associated with BP.All investigated COMT variants were strongly associated with the effect of diuretics, CCBs, and ARBs on SBP or DBP (P < .05), showing an additive effect when occurring in combination. After Bonferroni correction the polymorphism rs4680 (ValMet) in COMT was significantly associated with lower SBP in participants treated with CCBs (P = .009) with an especially strong impact in elderly individuals (age ≥ 70) alone (Δ = -14.08 mm Hg, P = .0005).These results underline the important role of estrogens and catecholamines in hypertension and the importance of genotype dependent, age-related adjustments of calcium-channel blocker treatment.

Mots-clé
Age Factors, Aged, Aged, 80 and over, Aging/drug effects, Aging/genetics, Antihypertensive Agents/therapeutic use, Aromatase/genetics, Blood Pressure/drug effects, Blood Pressure/genetics, Blood Pressure/physiology, Calcium Channel Blockers/therapeutic use, Catechol O-Methyltransferase/genetics, Cohort Studies, Female, Genotyping Techniques, Glucuronosyltransferase/genetics, Humans, Male, Middle Aged, Pharmacogenomic Variants, Switzerland
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/09/2017 9:22
Dernière modification de la notice
20/08/2019 15:43
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