title: GNB3 and CREB1 gene polymorphisms combined with negative life events increase susceptibility to major depression in a Chinese Han population.
abstract: BACKGROUND
  Major depression (MD) is caused by a combination of genetic and environmental factors. In this study we investigated the interaction of variations in the G-protein beta 3 subunit (GNB3) and cAMP response element binding protein 1 (CREB1) genes with negative life events in the pathogenesis of MD. One GNB3 polymorphism (rs5443) and four CREB1 polymorphisms (rs2253206, rs2551941, rs6740584, rs11904814) were investigated based on known associations with MD.
  
  
  METHODS
  512 patients with MD and 513 control subjects were genotyped. The frequency and severity of negative life events were measured by the Life Events Scale (LES). Gene-environment interactions (G×E) were assessed using the generalized multifactor dimensionality reduction (GMDR) method.
  
  
  RESULTS
  Differences in GNB3 rs5443 allele frequencies and genotype distributions were observed between MD patients and controls. Significant G×E interactions were detected between negative life events and genotypic variation of all five single nucleotide polymorphisms (SNPs). Individuals carrying the T- allele of rs5443 (CC), A- allele of rs2253206 (GG), T- allele of rs2551941 (AA), C- allele of rs6740584 (TT) or G- allele of rs11904814 (TT) conferred susceptibility to MD in subjects only exposed to high-negative life events. However, individuals with the T+ allele of rs5443 (CT, TT) were susceptible to MD when exposed to low negative life events.
  
  
  CONCLUSIONS
  Interactions between GNB3, CREB1 and negative life events were revealed. Further evidence is provided about the role of the environment in genetic vulnerability to MD.
authors.affiliation: Psychology Department of the Public Health Institute of Harbin Medical University, Harbin, China.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Ma
authors.affiliation: Psychology Department of the Public Health Institute of Harbin Medical University, Harbin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Psychology Department of the Public Health Institute of Harbin Medical University, Harbin, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Psychology Department of the Public Health Institute of Harbin Medical University, Harbin, China.
authors.forename: Zhengxue
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Northwestern University Feinberg School of Medicine, Evanston, Illinois, United States of America.
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.affiliation: Psychology Department of the Public Health Institute of Harbin Medical University, Harbin, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Psychology Department of the Public Health Institute of Harbin Medical University, Harbin, China.
authors.forename: Xiuxian
authors.initials: X
authors.lastname: Yang
authors.affiliation: Medical Psychological Institute of the Second Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Xiongzhao
authors.initials: X
authors.lastname: Zhu
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jincai
authors.initials: J
authors.lastname: He
authors.affiliation: Peking union Medical College Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Affiliated Hosptial of Jining Medical University, Jining, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ban
authors.affiliation: The Second Affiliated Hosptial of Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Psychology Department of the Public Health Institute of Harbin Medical University, Harbin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sui
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003865:Major Depressive Disorder / Q000209:etiology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins