title: Lack of association between the corticotrophin-releasing hormone receptor 2 gene and panic disorder.
abstract: Panic disorder is classified as an anxiety disorder and affects 1-3% of the population. An individual suffering from such a disorder may experience unexpected recurrent panic attacks and fear of future attacks. Twin and family studies have pointed towards a strong heritability of the disorder. Stress response and anxiety are thought to be mediated, at least in part, by the corticotrophin-releasing hormone (CRH), which is known to be a regulator of the hypothalamic-pituitary-adrenal pathway. To search for markers conferring genetic susceptibility to panic disorder, we typed three polymorphisms of the CRHR2 gene - CRHR2(CA), CRHR2(GT), and CRHR2(GAT) - in 466 individuals, 183 of whom had DSM-IV panic disorder. Seventy-five case-controls and 101 triad families plus 13 siblings were examined. Case-control association analyses using chi(2) tests yielded no difference in the distribution of the alleles. Linkage analysis using the Transmission Disequilibrium Test showed no preferential transmission of alleles for any of the three markers. Haplotype analysis indicated that allele 7 of CRHR2 (GAT) and 8 of CRHR2 (GT) are in almost complete linkage disequilibrium (P = 0.000 000 1). Although both neurobiology and chromosomal location point to the CHRH2 receptor gene as a candidate for panic disorder, our study indicates that the CRHR2 polymorphisms examined do not confer susceptibility to panic disorder. Further studies investigating additional polymorphisms in this gene and other components of the CRH signalling system may prove useful.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Canada.
authors.forename: Subi
authors.initials: S
authors.lastname: Tharmalingam
authors.forename: Nicole
authors.initials: N
authors.lastname: King
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Claudia
authors.initials: C
authors.lastname: Rothe
authors.forename: Diana
authors.initials: D
authors.lastname: Koszycki
authors.forename: Jacques
authors.initials: J
authors.lastname: Bradwejn
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D017931:DNA Primers; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D016584:Panic Disorder / Q000235:genetics*; D011110:Polymorphism, Genetic; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012016:Reference Values; D018433:Twin Studies as Topic
chemical_list: C101531:CRF receptor type 2; D017931:DNA Primers; D018019:Receptors, Corticotropin-Releasing Hormone