The Norepinephrine Transporter Gene SLC6A2 Variant Is Associated with Essential Hypertension

INTRODUCTION: The norepinephrine transporter, encoded by SLC6A2, terminates sympathetic signaling. The rs7194256 (C/T) 3′UTR variant has been implicated in altered NET regulation, yet evidence in essential hypertension and Turkish populations is limited.
METHODS: We conducted a hospital-based case–control study including 308 adults (153 essential hypertension; 155 normotensive controls). rs7194256 was genotyped by PCR – Restriction fragment length polymorphism analysis. Associations with hypertension (logistic regression) and with clinical/echocardiographic traits (linear regression) were tested under genotype (3-level), dominant (CT+TT vs CC), and additive (per-T-allele) models. Hardy–Weinberg expectations were met in controls (p=0.76) and in cases (p=0.93).
RESULTS: Genotype frequencies (CC, CT, and TT) were 54.9%, 38.6%, and 6.5% in cases, and 68.4%, 29.0%, and 2.6% in controls, respectively. Under the dominant model, CT+TT carriers had higher odds of hypertension than CC (adjusted OR 2.00, 95% CI 1.14–3.52, p=0.016). For individual genotypes, adjusted ORs were 1.90 (1.05 – 3.44, p=0.035) for CT vs CC and 2.86 (0.79–10.33, p=0.109) for TT vs CC. The T allele frequency was 25.8% in cases vs 17.1% in controls, with an adjusted allelic OR=1.84 (1.18–2.85, p=0.012). Systolic blood pressure differed across CC/CT/TT (adjusted p=0.028) and was higher in CT+TT vs CC (adjusted p = 0.029). Diastolic blood pressure showed an overall genotype association (adjusted p=0.035) but was not significant in the dominant model (p=0.096). Arterial stiffness indices and echocardiographic parameters showed no significant associations after adjustment.
DISCUSSION AND CONCLUSION: In this Turkish population, the SLC6A2 rs7194256 T allele is associated with essential hypertension and relates more strongly to systolic than diastolic phenotypes.

Keywords: SLC6A2, Norepinephrine transporter, Genetic polymorphism, Essential hypertension