1. Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder.
- Author
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Okamura N, Hashimoto K, Iyo M, Shimizu E, Dempfle A, Friedel S, and Reinscheid RK
- Subjects
- Adult, Attention Deficit Disorder with Hyperactivity psychology, Family, Female, Gene Frequency, Genotype, Germany epidemiology, Humans, Japan epidemiology, Male, Middle Aged, Panic Disorder psychology, Polymorphism, Single Nucleotide, Reverse Transcriptase Polymerase Chain Reaction, Schizophrenic Psychology, Sex Characteristics, Attention Deficit Disorder with Hyperactivity genetics, Panic Disorder genetics, Polymorphism, Genetic genetics, Receptors, G-Protein-Coupled genetics, Schizophrenia genetics
- Abstract
Panic disorder is a common anxiety disorder characterized by sudden and recurrent panic attacks. Previous studies have indicated significant genetic contributions and a susceptibility locus for panic disorder has been mapped to human chromosome 7p 15. The receptor for Neuropeptide S (NPS) is located in the same genomic region while NPS is known to produce arousal and anxiolytic-like effects in rodents. Here we report that a coding polymorphism in the Neuropeptide S receptor (NPSR) is associated with panic disorder in male patients of Japanese ancestry. The polymorphism (Asn(107)Ile) results in a gain-of-function of the receptor protein by increasing the agonist sensitivity about tenfold. The allele representing the less active isoform (NPSR Asn(107)) was found under-represented in male panic disorder patients, indicating a potential protective function of the protein. Two unrelated groups of patients diagnosed with schizophrenia or attention-deficit/hyperactivity disorder (ADHD) showed no association of particular NPSR alleles with the disorders. These results provide evidence for a gender-specific effect of NPSR in the pathogenesis of panic disorder.
- Published
- 2007
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