Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder

Pino Alonso, Mónica Gratacós, Cinto Segalàs, Georgia Escaramís, Eva Real, Mónica Bayés, Javier Labad, Clara López-Solà, Xavier P. Estivill, José M. Menchón

Research output: Contribution to journalArticle

30 Citations (Scopus)

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. Limitations: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)273-281
Number of pages9
JournalJournal of Psychiatry and Neuroscience
Volume37
Issue number4
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Fingerprint

Obsessive-Compulsive Disorder
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Genes
Single Nucleotide Polymorphism
N-methylglutamate
3' Untranslated Regions
Haplotypes
Tic Disorders
Confidence Intervals
Obsessive Behavior
Inborn Genetic Diseases
Genetic Predisposition to Disease
Blood Donors
Neuroimaging
Spain
Sample Size
Case-Control Studies
Dissection
Exons

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

Alonso, P., Gratacós, M., Segalàs, C., Escaramís, G., Real, E., Bayés, M., ... Menchón, J. M. (2012). Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder. Journal of Psychiatry and Neuroscience, 37(4), 273-281. https://doi.org/10.1503/jpn.110109

Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder. / Alonso, Pino; Gratacós, Mónica; Segalàs, Cinto; Escaramís, Georgia; Real, Eva; Bayés, Mónica; Labad, Javier; López-Solà, Clara; Estivill, Xavier P.; Menchón, José M.

In: Journal of Psychiatry and Neuroscience, Vol. 37, No. 4, 06.2012, p. 273-281.

Research output: Contribution to journalArticle

Alonso, P, Gratacós, M, Segalàs, C, Escaramís, G, Real, E, Bayés, M, Labad, J, López-Solà, C, Estivill, XP & Menchón, JM 2012, 'Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder', Journal of Psychiatry and Neuroscience, vol. 37, no. 4, pp. 273-281. https://doi.org/10.1503/jpn.110109
Alonso, Pino ; Gratacós, Mónica ; Segalàs, Cinto ; Escaramís, Georgia ; Real, Eva ; Bayés, Mónica ; Labad, Javier ; López-Solà, Clara ; Estivill, Xavier P. ; Menchón, José M. / Association between the NMDA glutamate receptor GRIN2B gene and obsessive-compulsive disorder. In: Journal of Psychiatry and Neuroscience. 2012 ; Vol. 37, No. 4. pp. 273-281.
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AU - Real, Eva

AU - Bayés, Mónica

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