Gene-based SNP genetic association study of the corticotropin-releasing hormone receptor-2 (CRHR2) in major depression.
An increasing amount of data suggests that affective disorders are related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the stress-response system. Corticotropin-releasing hormone receptor-2 (CRHR2)-deficient mice display a stress-sensitive and anxiety-like phenotype suggesting that the CRHR2 is a plausible functional candidate gene influencing the reactivity of the HPA axis and therefore the liability to develop affective disorders. In this study, a gene-based single nucleotide polymorphism (SNP) map of the corticotropin-releasing hormone receptor 2 (CRHR2) was constructed containing one synonymous cSNP in exon 10, two intronic SNPs, and two SNPs in the 5' upstream regulatory region. No significant difference in allele or genotype frequency was found for four out of the five SNPs between Belgian unipolar (UP) patients and age-, gender-, and ethnicity-matched controls. The cSNP did show allelic and genotypic association with borderline significance (P=0.04). However, a replication study of this cSNP in a bipolar sample of Belgian origin and a Swedish UP sample did not show significant differences in allele and genotype frequencies.
Villafuerte
Sandra M
SM
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
Del-Favero
Jurgen
J
Adolfsson
Rolf
R
Souery
Daniel
D
Massat
Isabelle
I
Mendlewicz
Julien
J
Van Broeckhoven
Christine
C
Claes
Stephan
S
D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003866:Depressive Disorder / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*
D018019:Receptors, Corticotropin-Releasing Hormone; D004247:DNA