The norepinephrine transporter gene is a candidate gene for panic disorder

Abstract

Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks with a lifetime prevalence of 4.7%. Genetic factors are known to contribute to the development of the disorder. Several lines of evidence point towards a major role of the norepinephrine system in the pathogenesis of PD. The SLC6A2 gene is located on chromosome 16q12.2 and encodes the norepinephrine transporter (NET), responsible for the reuptake of norepinephrine into presynaptic nerve terminals. The aim of the present study was to analyze genetic variants located within the NET gene for association with PD. The case-control sample consisted of 449 patients with PD and 279 ethnically matched controls. All cases fulfilled the ICD-10 diagnostic criteria for PD. Genotyping was performed using the Sequenom platform (Sequenom, Inc, San Diego, USA). To test for allelic and haplotypic association, the PLINK software was used, and COMBASSOC was applied to test for gene-wise association. After quality control 29 single nucleotide polymorphisms (SNPs) spanning the gene-region were successfully analyzed. Seven SNPs located within the 5' end of the gene were significantly associated with PD. Furthermore, the NET gene showed overall evidence for association with the disease (P = 0.000035). In conclusion, the present study indicates that NET could be a susceptibility gene for PD.