Dataset Information

Association Between the SLC1A1 Glutamate Transporter Gene and Obsessive-Compulsive Disorder in the Chinese Han Population.

ABSTRACT:

Background

Obsessive-compulsive disorder (OCD) is a common, serious and genetically related mental illness; the etiology of OCD has not yet reached a definitive conclusion. Multiple evidence suggests that the glutamatergic system plays a major role in the pathophysiology of OCD. However, subsequent studies on the glutamate transporter gene are not consistent. OCD is a heterogeneous disease. To resolve the complex genetic basis of OCD, division the disorder into different subphenotypes is an effective method for studying the pathogenesis of OCD.

Methods

We recruited 438 OCD patients and 465 age- and sex-matched controls from a Chinese Han population. rs10491734, rs3780412, rs301434 and rs3087879 SNPs were genotyped by real-time TaqMan polymerase chain reaction, and the chi-squared test was used to compare allele and genotype frequencies of variants between the two groups.

Results

The genotype of rs301434 was statistically significant in total patients with OCD and the controls. After grouping by age and gender, the genotype of rs301434 was statistically significant in early-onset OCD, late-onset OCD as well as male OCD, the allele and genotype of rs3780412 was associated with late-onset OCD. Haplotype analysis showed that four loci haplotypes (G-A-A-G and G-G-A-G) were associated with total OCD, (G-G-A-G) was associated with female OCD, (G-A-G-G) was associated with male OCD, (G-A-A-G and G-G-A-G) were associated with late-onset OCD.

Conclusion

This study provides suggestive evidence that SLC1A1 may be involved in the development of OCD in the Han population. However, these findings require further replication.

SUBMITTER: Huang X

PROVIDER: S-EPMC7872936 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Association Between the <i>SLC1A1</i> Glutamate Transporter Gene and Obsessive-Compulsive Disorder in the Chinese Han Population.

Huang Xing X Liu Jie J Cong Jinzhi J Zhang Xinhua X

Neuropsychiatric disease and treatment 20210205

<h4>Background</h4>Obsessive-compulsive disorder (OCD) is a common, serious and genetically related mental illness; the etiology of OCD has not yet reached a definitive conclusion. Multiple evidence suggests that the glutamatergic system plays a major role in the pathophysiology of OCD. However, subsequent studies on the glutamate transporter gene are not consistent. OCD is a heterogeneous disease. To resolve the complex genetic basis of OCD, division the disorder into different subphenotypes is ...[more]

PMID: 33574671

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Project description: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.