title: Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder.
abstract: BACKGROUND
  Recent data from neuroimaging, genetic and clinical trials and animal models suggest a role for altered glutamatergic neuro transmission in the pathogenesis of obsessive-compulsive disorder (OCD). The aim of this study was to investigate whether variants in the GRIN2B gene, the gene encoding the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor, may contribute to genetic susceptibility to OCD or to different OCD subphenotypes.
  
  
  METHODS
  Between 2003 and 2008, we performed a case-control association study in which we genotyped 10 tag single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3' UTR) of GRIN2B. We performed SNP association and haplotype analysis considering the OCD diagnosis and different OCD subphenotypes: early-onset OCD, comorbid tic disorders and OCD clinical symptom dimensions.
  
  
  RESULTS
  We enrolled 225 patients with OCD and 279 controls recruited from the OCD Clinic at Bellvitge Hospital (Barcelona, Spain). No significant difference in the distribution of alleles or genotypes was detected between patients with OCD and controls. Nonetheless, on analyzing OCD subphenotypes, the rs1805476 SNP in male patients (95% confidence interval [CI] 1.37-4.22, p = 0.002) and a 4-SNP haplotype in the whole sample (rs1805476, rs1805501, rs1805502 and rs1805477; odds ratio 1.92, 95% CI 1.22-3.01; permutation p = 0.023) were significantly associated with the presence of contamination obsessions and cleaning compulsions.
  
  
  CONCLUSIONS
  Study limitations included the risk of population stratification associated with the case-control design, use of psychiatrically unscreened blood donors as the control group, reduced sample size of participants with certain OCD subphenotypes and tested polymorphisms limited to 3' UTR and exon 13 of GRIN2B.
  
  
  CONCLUSIONS
  Our results converge with recent data suggesting a possible contribution of glutamatergic variants to the genetic vulnerability to OCD or at least to certain OCD manifestations. The dissection of OCD into more homogeneous subphenotypes may constitute a useful tool to disentangle the complex genetic basis of the disorder.
authors.affiliation: OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain. mpalonso@bellvitgehospital.cat
authors.forename: Pino
authors.initials: P
authors.lastname: Alonso
authors.forename: Mónica
authors.initials: M
authors.lastname: Gratacós
authors.forename: Cinto
authors.initials: C
authors.lastname: Segalàs
authors.forename: Georgia
authors.initials: G
authors.lastname: Escaramís
authors.forename: Eva
authors.initials: E
authors.lastname: Real
authors.forename: Mónica
authors.initials: M
authors.lastname: Bayés
authors.forename: Javier
authors.initials: J
authors.lastname: Labad
authors.forename: Clara
authors.initials: C
authors.lastname: López-Solà
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: José M
authors.initials: JM
authors.lastname: Menchón
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate