title: A study of N-methyl-D-aspartate receptor gene (GRIN2B) variants as predictors of treatment-resistant major depression.
abstract: BACKGROUND
  In clinical practice, ketamine, an antagonist of the N-methyl-D-aspartate receptor (NMDAR), is used to alleviate depressive symptoms in patients with major depressive disorder (MDD), especially in those with treatment-resistant depression (TRD). Accordingly, the human gene coding for the 2B subunit of the NMDAR (GRIN2B) is considered a promising candidate gene for MDD susceptibility.
  
  
  OBJECTIVE
  The primary aim of this study is to examine whether potentially functional polymorphisms of GRIN2B confer risk for MDD, and second to investigate whether GRIN2B acts as a genetic predictor for TRD in MDD patients.
  
  
  METHODS
  We enrolled 178 TRD and 612 non-TRD patients as well as 779 healthy controls.
  
  
  RESULTS
  Four potentially functional polymorphisms (rs1805502, rs890, rs1806201, and rs7301328) within GRIN2B were genotyped in all participants. The haplotype analysis found significant differences in the distribution of the G-T haplotype between the TRD and control groups (corrected P = 0.007), and the frequency of the G-T haplotype in TRD group was significantly higher than that in the controls (TRD/control ratio 0.31:0.21). Statistically significant differences in allele and genotype frequencies were detected between TRD and non-TRD groups for the rs1805502 polymorphism within GRIN2B. There was a significant allelic association between rs1805502 and TRD with an excess of the G allele in the TRD group, compared to non-TRD group (OR = 1.55, 95 % CI = 1.18-2.05, corrected P = 0.008).
  
  
  CONCLUSIONS
  These initial findings strengthen the hypothesis that GRIN2B not only confers susceptibility to TRD, but also plays a genetic predictor for TRD in MDD patients.
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Zezhi
authors.initials: Z
authors.lastname: Li
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Zuowei
authors.initials: Z
authors.lastname: Wang
authors.forename: Daihui
authors.initials: D
authors.lastname: Peng
authors.forename: Wu
authors.initials: W
authors.lastname: Hong
authors.forename: Chengmei
authors.initials: C
authors.lastname: Yuan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Shunying
authors.initials: S
authors.lastname: Yu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Zeping
authors.initials: Z
authors.lastname: Xiao
authors.forename: Yiru
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000235:genetics*; D061218:Depressive Disorder, Treatment-Resistant / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate