Polymorphism of the norepinephrine transporter (SLC6A2) gene not related to cardiac sympathetic activity in heart failure patients

Objectives The norepinephrine (NE) transporter (uptake-1), encoded by the SLC6A2 gene, is responsible for reuptake of NE into presynaptic nerve terminals and regulates NE homeostasis. However, it is unknown if polymorphisms of SLC6A2 influence cardiac myocardial sympathetic activity. 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy has been extensively validated and clinically used to evaluate cardiac sympathetic function in different cardiac diseases. The influence of SLC6A2 single-nucleotide polymorphisms (SNP) on the 123I-mIBG scintigraphy parameters in patients with heart failure (HF) was studied.

Methods Forty-nine patients with stable HF (age 66.5±8.1 years, LVEF 22.3±6.4 and functional class NYHA 2.3±0.4) referred for 123I-mIBG scintigraphy were enrolled. Fifteen minutes (early H/M) and 4 hours (late H/M) after administration of 185 MBq 123I-mIBG anterior planar thoracic images were acquired using a gamma-camera equipped with medium energy collimators. In addition, washout (WO) was calculated. DNA was extracted from whole-blood samples. Fourteen exons of the SLC6A2 gene were analysed.

Results The mean early H/M was 2.10±0.39, late H/M 1.81±0.39 and WO 13.7±11.2. Six different SLC6A2 SNPs were identified. Only one SNP was in the coding region but did not cause a change in amino acid formation. The other 5 SNPs were intronic and were predicted not to affect splicing. Only the LVEF was an independent predictor of early H/M (adjusted R2 = 0.063, p = 0.045) and late H/M (adjusted R2 = 0.116, p = 0.010). For WO the NT-proBNP was the only independent predictor (adjusted R2 = 0.074, p = 0.032). SLC6A2 SNPs and NYHA class were not related to early H/M, late H/M and WO.

Conclusions As far as we know this is the first study investigating the association between SLC6A2 gene polymorphism and cardiac sympathetic activity. In this specific HF population polymorphism of SLC6A2 did not explain for variations in cardiac sympathetic activity.