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

被引:44
作者
Alonso, Pino [1 ,2 ,3 ]
Gratacos, Monica [4 ,5 ]
Segalas, Cinto [1 ,2 ]
Escaramis, Georgia [4 ,5 ]
Real, Eva [1 ,2 ,6 ,7 ,8 ]
Bayes, Monica
Labad, Javier [9 ]
Lopez-Sola, Clara [1 ,2 ]
Estivill, Xavier [4 ,5 ,10 ]
Menchon, Jose M. [1 ,2 ,3 ]
机构
[1] Bellvitge Univ Hosp, Dept Psychiat, OCD Clin & Res Unit, Barcelona 08907, Spain
[2] Inst Salud Carlos III, CIBERSAM, Madrid, Spain
[3] Univ Barcelona, Dept Clin Sci, Barcelona, Spain
[4] Inst Salud Carlos III, CIBERESP Epidemiol & Salud Publ CIBERESP, Barcelona, Spain
[5] Barcelona Biomed Res Pk, Ctr Genom Regulat, Genes & Dis Program, Barcelona, Spain
[6] IDIBELL, Barcelona, Spain
[7] CRG, Genom Core Facil, Barcelona, Spain
[8] CRG, Ctr Nacl Genotipado CeGen, Barcelona, Spain
[9] Univ Rovira & Virgili, IISPV, Hosp Psiquiat Univ Inst Pere Mata, E-43201 Reus, Spain
[10] Pompeu Fabra Univ, Expt & Hlth Sci Dept, Barcelona, Spain
来源
JOURNAL OF PSYCHIATRY & NEUROSCIENCE | 2012年 / 37卷 / 04期
关键词
COMORBID TOURETTES-SYNDROME; TRANSPORTER GENE; PHENOTYPIC-EXPRESSION; SYMPTOM DIMENSIONS; TRANSGENIC MODEL; GENDER; SLC1A1; SCALE; OCD; TRANSMISSION;
D O I
10.1503/jpn.110109
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:273 / 281
页数:9
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