A functional variant of the NEDD4L gene is associated with beneficial treatment response with β-blockers and diuretics in hypertensive patients.
(2011) In Journal of Hypertension 29(2). p.388-395- Abstract
- OBJECTIVE: The capability of the protein NEDD4L to reduce renal tubular expression of epithelial Na+ channel (ENaC) is influenced by a functional rs4149601 G→A NEDD4L polymorphism. As diuretics and β-blockers inhibit renal sodium reabsorption and renin release, respectively, we hypothesized that the β-blocker or diuretic-induced blood pressure reduction and prevention of cardiovascular disease would be greater in patients with the highest ENaC expression (rs4149601 G-allele), whereas there would be no such genetically mediated differences in treatment efficacy among patients treated with the vasodilator diltiazem. METHODS: We related rs4149601 status to 6-month blood pressure reduction and risk of cardiovascular events in 5152 hypertensive... (More)
- OBJECTIVE: The capability of the protein NEDD4L to reduce renal tubular expression of epithelial Na+ channel (ENaC) is influenced by a functional rs4149601 G→A NEDD4L polymorphism. As diuretics and β-blockers inhibit renal sodium reabsorption and renin release, respectively, we hypothesized that the β-blocker or diuretic-induced blood pressure reduction and prevention of cardiovascular disease would be greater in patients with the highest ENaC expression (rs4149601 G-allele), whereas there would be no such genetically mediated differences in treatment efficacy among patients treated with the vasodilator diltiazem. METHODS: We related rs4149601 status to 6-month blood pressure reduction and risk of cardiovascular events in 5152 hypertensive patients (DBP ≥ 100 mmHg) from the Nordic Diltiazem Study (NORDIL) randomized to either β-blocker and/or diuretic-based treatment or diltiazem-based treatment. RESULTS: In patients on β-blocker or diuretic monotherapy, carriers of the G-allele had greater SBP reduction (19.5 ± 16.8 vs. 15.0 ± 19.3 mmHg, P < 0.001) and DBP reduction (15.4 ± 8.3vs. 14.1 ± 8.4 mmHg, P = 0.02) and during 4.5 years of follow-up among patients randomized to β-blockers and/or diuretics, carriers of the G-allele had greater protection from cardiovascular events [relative risk (RR) = 0.52, 95% confidence interval (CI) = 0.36-0.74, P < 0.001] as compared to AA homozygotes. Within the diltiazem group, there was no difference in blood pressure reduction or risk of cardiovascular events according to genotype. CONCLUSION: The functional NEDD4L rs4149601 polymorphism influences the efficacy of β-blocker and/or diuretic-based antihypertensive treatment both in terms of blood pressure reduction and cardiovascular disease protection, whereas diltiazem-based antihypertensive treatment efficacy is not influenced by this NEDD4L polymorphism. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1732300
- author
- Svensson, Patrik LU ; Wahlstrand, Björn ; Almgren, Peter LU ; Dahlberg, Jonas LU ; Fava, Cristiano LU ; Kjeldsen, Sverre ; Hedner, Thomas and Melander, Olle LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- hypertension treatment, ENaC, NORDIL, pharmacogenetics
- in
- Journal of Hypertension
- volume
- 29
- issue
- 2
- pages
- 388 - 395
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000285744600030
- pmid:21052022
- scopus:78651273887
- pmid:21052022
- ISSN
- 1473-5598
- DOI
- 10.1097/HJH.0b013e3283410390
- language
- English
- LU publication?
- yes
- id
- 9ecf3360-b098-489c-bfbd-7a46fad6e564 (old id 1732300)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21052022?dopt=Abstract
- date added to LUP
- 2016-04-01 13:54:49
- date last changed
- 2024-03-13 11:12:18
@article{9ecf3360-b098-489c-bfbd-7a46fad6e564, abstract = {{OBJECTIVE: The capability of the protein NEDD4L to reduce renal tubular expression of epithelial Na+ channel (ENaC) is influenced by a functional rs4149601 G→A NEDD4L polymorphism. As diuretics and β-blockers inhibit renal sodium reabsorption and renin release, respectively, we hypothesized that the β-blocker or diuretic-induced blood pressure reduction and prevention of cardiovascular disease would be greater in patients with the highest ENaC expression (rs4149601 G-allele), whereas there would be no such genetically mediated differences in treatment efficacy among patients treated with the vasodilator diltiazem. METHODS: We related rs4149601 status to 6-month blood pressure reduction and risk of cardiovascular events in 5152 hypertensive patients (DBP ≥ 100 mmHg) from the Nordic Diltiazem Study (NORDIL) randomized to either β-blocker and/or diuretic-based treatment or diltiazem-based treatment. RESULTS: In patients on β-blocker or diuretic monotherapy, carriers of the G-allele had greater SBP reduction (19.5 ± 16.8 vs. 15.0 ± 19.3 mmHg, P < 0.001) and DBP reduction (15.4 ± 8.3vs. 14.1 ± 8.4 mmHg, P = 0.02) and during 4.5 years of follow-up among patients randomized to β-blockers and/or diuretics, carriers of the G-allele had greater protection from cardiovascular events [relative risk (RR) = 0.52, 95% confidence interval (CI) = 0.36-0.74, P < 0.001] as compared to AA homozygotes. Within the diltiazem group, there was no difference in blood pressure reduction or risk of cardiovascular events according to genotype. CONCLUSION: The functional NEDD4L rs4149601 polymorphism influences the efficacy of β-blocker and/or diuretic-based antihypertensive treatment both in terms of blood pressure reduction and cardiovascular disease protection, whereas diltiazem-based antihypertensive treatment efficacy is not influenced by this NEDD4L polymorphism.}}, author = {{Svensson, Patrik and Wahlstrand, Björn and Almgren, Peter and Dahlberg, Jonas and Fava, Cristiano and Kjeldsen, Sverre and Hedner, Thomas and Melander, Olle}}, issn = {{1473-5598}}, keywords = {{hypertension treatment; ENaC; NORDIL; pharmacogenetics}}, language = {{eng}}, number = {{2}}, pages = {{388--395}}, publisher = {{Lippincott Williams & Wilkins}}, series = {{Journal of Hypertension}}, title = {{A functional variant of the NEDD4L gene is associated with beneficial treatment response with β-blockers and diuretics in hypertensive patients.}}, url = {{http://dx.doi.org/10.1097/HJH.0b013e3283410390}}, doi = {{10.1097/HJH.0b013e3283410390}}, volume = {{29}}, year = {{2011}}, }