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

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.