A polymorphism in the noradrenaline transporter gene is associated with increased blood pressure in patients with resistant hypertension

Nina Eikelis, Francine Z. Marques, Dagmara Hering, Petra Marusic, Geoffrey A. Head, Antony S. Walton, Elisabeth A. Lambert, Murray D. Esler, Carolina I. Sari, Markus P. Schlaich, Gavin W. Lambert

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives: Noradrenaline released from sympathetic nerves is rapidly inactivated via the action of the noradrenaline transporter (NET). We aimed to determine whether a single nucleotide polymorphism (SNP) in the NET gene, rs7194256, was associated with blood pressure and plasma noradrenaline concentration in patients with resistant hypertension. Methods: Ninety-two consecutive patients with resistant hypertension participated in this study (age 62±1.3 years, BMI 32±0.6kg/m 2, mean±SEM). Blood pressure was assessed using 24-h ambulatory blood pressure monitoring. Genotyping of rs7194256 (C/T) was performed using a predeveloped TaqMan SNP Genotyping Assay. Plasma catecholamines were analyzed using high-performance liquid chromatography. Results: There were no differences in anthropometric measures between those carrying a T allele or the CC genotype. Patients carrying a T allele had significantly higher SBP: 24-h mean 148±2.6 vs. 140±2.4; 24-h max 189±3.2 vs. 179±2.6; 24-h min 114±3.0 vs. 105±2.3; night mean 141±3.0 vs. 131±2.5; night max 170±3.6 vs. 159±3.1; night min 118±3.4 vs. 109±2.4 (all P<0.05). T-allele carriers had a significantly higher arterial noradrenaline concentration: 573±53 vs. 377±35pg/ml (P=0.002) and lower ratio of the intraneuronal noradrenaline metabolite, 3,4-dihydroxyphenylglycol, to noradrenaline (3.01±0.4 vs. 4.08±0.3pg/ml; P=0.024). Conclusion: A SNP in the NET gene in patients with resistant hypertension is associated with higher plasma noradrenaline concentration and elevated SBP. Impaired NET function may be a contributor to the pronounced activation of the sympathetic nervous system characteristic of patients with resistant hypertension.

Original languageEnglish
Pages (from-to)1571-1577
Number of pages7
JournalJournal of Hypertension
Volume36
Issue number7
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • blood pressure
  • noradrenaline
  • noradrenaline transporter
  • resistant hypertension
  • single nucleotide polymorphism

Cite this

Eikelis, Nina ; Marques, Francine Z. ; Hering, Dagmara ; Marusic, Petra ; Head, Geoffrey A. ; Walton, Antony S. ; Lambert, Elisabeth A. ; Esler, Murray D. ; Sari, Carolina I. ; Schlaich, Markus P. ; Lambert, Gavin W. / A polymorphism in the noradrenaline transporter gene is associated with increased blood pressure in patients with resistant hypertension. In: Journal of Hypertension. 2018 ; Vol. 36, No. 7. pp. 1571-1577.
@article{7882d98bafad4c24ad8b3e5d92a30cf8,
title = "A polymorphism in the noradrenaline transporter gene is associated with increased blood pressure in patients with resistant hypertension",
abstract = "Objectives: Noradrenaline released from sympathetic nerves is rapidly inactivated via the action of the noradrenaline transporter (NET). We aimed to determine whether a single nucleotide polymorphism (SNP) in the NET gene, rs7194256, was associated with blood pressure and plasma noradrenaline concentration in patients with resistant hypertension. Methods: Ninety-two consecutive patients with resistant hypertension participated in this study (age 62±1.3 years, BMI 32±0.6kg/m 2, mean±SEM). Blood pressure was assessed using 24-h ambulatory blood pressure monitoring. Genotyping of rs7194256 (C/T) was performed using a predeveloped TaqMan SNP Genotyping Assay. Plasma catecholamines were analyzed using high-performance liquid chromatography. Results: There were no differences in anthropometric measures between those carrying a T allele or the CC genotype. Patients carrying a T allele had significantly higher SBP: 24-h mean 148±2.6 vs. 140±2.4; 24-h max 189±3.2 vs. 179±2.6; 24-h min 114±3.0 vs. 105±2.3; night mean 141±3.0 vs. 131±2.5; night max 170±3.6 vs. 159±3.1; night min 118±3.4 vs. 109±2.4 (all P<0.05). T-allele carriers had a significantly higher arterial noradrenaline concentration: 573±53 vs. 377±35pg/ml (P=0.002) and lower ratio of the intraneuronal noradrenaline metabolite, 3,4-dihydroxyphenylglycol, to noradrenaline (3.01±0.4 vs. 4.08±0.3pg/ml; P=0.024). Conclusion: A SNP in the NET gene in patients with resistant hypertension is associated with higher plasma noradrenaline concentration and elevated SBP. Impaired NET function may be a contributor to the pronounced activation of the sympathetic nervous system characteristic of patients with resistant hypertension.",
keywords = "blood pressure, noradrenaline, noradrenaline transporter, resistant hypertension, single nucleotide polymorphism",
author = "Nina Eikelis and Marques, {Francine Z.} and Dagmara Hering and Petra Marusic and Head, {Geoffrey A.} and Walton, {Antony S.} and Lambert, {Elisabeth A.} and Esler, {Murray D.} and Sari, {Carolina I.} and Schlaich, {Markus P.} and Lambert, {Gavin W.}",
year = "2018",
month = "7",
day = "1",
doi = "10.1097/HJH.0000000000001736",
language = "English",
volume = "36",
pages = "1571--1577",
journal = "Journal of Hypertension",
issn = "0263-6352",
publisher = "Lippincott Williams & Wilkins",
number = "7",

}

A polymorphism in the noradrenaline transporter gene is associated with increased blood pressure in patients with resistant hypertension. / Eikelis, Nina; Marques, Francine Z.; Hering, Dagmara; Marusic, Petra; Head, Geoffrey A.; Walton, Antony S.; Lambert, Elisabeth A.; Esler, Murray D.; Sari, Carolina I.; Schlaich, Markus P.; Lambert, Gavin W.

In: Journal of Hypertension, Vol. 36, No. 7, 01.07.2018, p. 1571-1577.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A polymorphism in the noradrenaline transporter gene is associated with increased blood pressure in patients with resistant hypertension

AU - Eikelis, Nina

AU - Marques, Francine Z.

AU - Hering, Dagmara

AU - Marusic, Petra

AU - Head, Geoffrey A.

AU - Walton, Antony S.

AU - Lambert, Elisabeth A.

AU - Esler, Murray D.

AU - Sari, Carolina I.

AU - Schlaich, Markus P.

AU - Lambert, Gavin W.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Objectives: Noradrenaline released from sympathetic nerves is rapidly inactivated via the action of the noradrenaline transporter (NET). We aimed to determine whether a single nucleotide polymorphism (SNP) in the NET gene, rs7194256, was associated with blood pressure and plasma noradrenaline concentration in patients with resistant hypertension. Methods: Ninety-two consecutive patients with resistant hypertension participated in this study (age 62±1.3 years, BMI 32±0.6kg/m 2, mean±SEM). Blood pressure was assessed using 24-h ambulatory blood pressure monitoring. Genotyping of rs7194256 (C/T) was performed using a predeveloped TaqMan SNP Genotyping Assay. Plasma catecholamines were analyzed using high-performance liquid chromatography. Results: There were no differences in anthropometric measures between those carrying a T allele or the CC genotype. Patients carrying a T allele had significantly higher SBP: 24-h mean 148±2.6 vs. 140±2.4; 24-h max 189±3.2 vs. 179±2.6; 24-h min 114±3.0 vs. 105±2.3; night mean 141±3.0 vs. 131±2.5; night max 170±3.6 vs. 159±3.1; night min 118±3.4 vs. 109±2.4 (all P<0.05). T-allele carriers had a significantly higher arterial noradrenaline concentration: 573±53 vs. 377±35pg/ml (P=0.002) and lower ratio of the intraneuronal noradrenaline metabolite, 3,4-dihydroxyphenylglycol, to noradrenaline (3.01±0.4 vs. 4.08±0.3pg/ml; P=0.024). Conclusion: A SNP in the NET gene in patients with resistant hypertension is associated with higher plasma noradrenaline concentration and elevated SBP. Impaired NET function may be a contributor to the pronounced activation of the sympathetic nervous system characteristic of patients with resistant hypertension.

AB - Objectives: Noradrenaline released from sympathetic nerves is rapidly inactivated via the action of the noradrenaline transporter (NET). We aimed to determine whether a single nucleotide polymorphism (SNP) in the NET gene, rs7194256, was associated with blood pressure and plasma noradrenaline concentration in patients with resistant hypertension. Methods: Ninety-two consecutive patients with resistant hypertension participated in this study (age 62±1.3 years, BMI 32±0.6kg/m 2, mean±SEM). Blood pressure was assessed using 24-h ambulatory blood pressure monitoring. Genotyping of rs7194256 (C/T) was performed using a predeveloped TaqMan SNP Genotyping Assay. Plasma catecholamines were analyzed using high-performance liquid chromatography. Results: There were no differences in anthropometric measures between those carrying a T allele or the CC genotype. Patients carrying a T allele had significantly higher SBP: 24-h mean 148±2.6 vs. 140±2.4; 24-h max 189±3.2 vs. 179±2.6; 24-h min 114±3.0 vs. 105±2.3; night mean 141±3.0 vs. 131±2.5; night max 170±3.6 vs. 159±3.1; night min 118±3.4 vs. 109±2.4 (all P<0.05). T-allele carriers had a significantly higher arterial noradrenaline concentration: 573±53 vs. 377±35pg/ml (P=0.002) and lower ratio of the intraneuronal noradrenaline metabolite, 3,4-dihydroxyphenylglycol, to noradrenaline (3.01±0.4 vs. 4.08±0.3pg/ml; P=0.024). Conclusion: A SNP in the NET gene in patients with resistant hypertension is associated with higher plasma noradrenaline concentration and elevated SBP. Impaired NET function may be a contributor to the pronounced activation of the sympathetic nervous system characteristic of patients with resistant hypertension.

KW - blood pressure

KW - noradrenaline

KW - noradrenaline transporter

KW - resistant hypertension

KW - single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=85048310456&partnerID=8YFLogxK

U2 - 10.1097/HJH.0000000000001736

DO - 10.1097/HJH.0000000000001736

M3 - Article

VL - 36

SP - 1571

EP - 1577

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 7

ER -