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

作者：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.

来源：Journal of Hypertension, 2018, 36(7): 1571-1577.

DOI：10.1097/HJH.0000000000001736

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

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 621.3 years, BMI 320.6kg/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.

• 出版日期2018-7