title: Interaction between CRHR1 and BDNF genes increases the risk of recurrent major depressive disorder in Chinese population.
abstract: BACKGROUND
  An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH) regulates brain-derived neurotrophic factor (BDNF) expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1) and BDNF genes in recurrent major depressive disorder (MDD).
  
  
  RESULTS
  The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). CRHR1 gene (rs1876828, rs242939 and rs242941) and BDNF gene (rs6265) were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022) with an Odds Ratio 0.454 (95% CI 0.266-0.775). A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05) using a generalized multifactor dimensionality reduction (GMDR) method.
  
  
  CONCLUSIONS
  Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD.
authors.affiliation: Institute of Neuropsychiatry, Wuhan University, Wuhan, China.
authors.forename: Zheman
authors.initials: Z
authors.lastname: Xiao
authors.forename: Wanhong
authors.initials: W
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.forename: Qirong
authors.initials: Q
authors.lastname: Wan
authors.forename: Can
authors.initials: C
authors.lastname: Yang
authors.forename: Huiling
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.forename: Gaohua
authors.initials: G
authors.lastname: Wang
authors.forename: Zhongchun
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003865:Major Depressive Disorder / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008957:Models, Genetic; D058011:Multifactor Dimensionality Reduction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012008:Recurrence; D012307:Risk Factors; D000099052:CRF Receptor, Type 1
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1