title: 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.
authors.affiliation: Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Skovagervej 2, 8240 Risskov, Denmark. henrbutt@rm.dk
authors.forename: H N
authors.initials: HN
authors.lastname: Buttenschøn
authors.forename: A S
authors.initials: AS
authors.lastname: Kristensen
authors.forename: H N
authors.initials: HN
authors.lastname: Buch
authors.forename: J H
authors.initials: JH
authors.lastname: Andersen
authors.forename: J P
authors.initials: JP
authors.lastname: Bonde
authors.forename: M
authors.initials: M
authors.lastname: Grynderup
authors.forename: A M
authors.initials: AM
authors.lastname: Hansen
authors.forename: H
authors.initials: H
authors.lastname: Kolstad
authors.forename: A
authors.initials: A
authors.lastname: Kaergaard
authors.forename: L
authors.initials: L
authors.lastname: Kaerlev
authors.forename: S
authors.initials: S
authors.lastname: Mikkelsen
authors.forename: J F
authors.initials: JF
authors.lastname: Thomsen
authors.forename: P
authors.initials: P
authors.lastname: Koefoed
authors.forename: A
authors.initials: A
authors.lastname: Erhardt
authors.forename: D P D
authors.initials: DP
authors.lastname: Woldbye
authors.forename: A D
authors.initials: AD
authors.lastname: Børglum
authors.forename: O
authors.initials: O
authors.lastname: Mors
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D016584:Panic Disorder / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D009638:Norepinephrine