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

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.Ninety-two consecutive patients with resistant hypertension participated in this study (age 62 ± 1.3 years, BMI 32 ± 0.6 kg/m, 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.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 ± 35 pg/ml (P = 0.002) and lower ratio of the intraneuronal noradrenaline metabolite, 3,4-dihydroxyphenylglycol, to noradrenaline (3.01 ± 0.4 vs. 4.08 ± 0.3 pg/ml; P = 0.024).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.