Key result
NET gene T allele linked to ~8 mmHg higher 24-h systolic BP in resistant hypertension.
Why the study?
The association between a single nucleotide polymorphism in the noradrenaline transporter gene and blood pressure and plasma noradrenaline concentration in resistant hypertension was investigated.
Is the T allele of the NET gene SNP rs7194256 associated with increased blood pressure and plasma noradrenaline in patients with resistant hypertension?
Observational (n=92)
Is the T allele of the NET gene SNP rs7194256 associated with increased blood pressure and plasma noradrenaline in patients with resistant hypertension?
Absolute Event Rate: 148% vs 140%
p-value: p=<0.05
A polymorphism in the NET gene (rs7194256 T allele) is associated with higher plasma noradrenaline and elevated systolic blood pressure in patients with resistant hypertension.
NET rs7194256 variant may link to BP control in resistant hypertension; leaves open causal role and need for prospective validation.
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 ± 0.6 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. 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 ± 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). 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.
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Eikelis et al. (2018) conducted an observational in resistant hypertension (n=92). rs7194256 T allele in the NET gene vs. CC genotype was evaluated on 24-h mean systolic blood pressure (p=<0.05). Carrying the rs7194256 T allele in the NET gene was associated with higher 24-h mean systolic blood pressure (148 vs 140 mmHg; P<0.05) in patients with resistant hypertension.
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