The role of GRIN2B in Tourette syndrome: Results from a transmission disequilibrium study

Background: Previous studies have indicated that dopamine interacts with glutamatergic projection neurons and that N-methyl-d-aspartate (NMDA) receptors might be involved in the pathogenesis of Tourette syndrome (TS). In this study, we examined whether two functional polymorphisms (rs1805476 and rs1805502) in the 3'UTR of the NMDA receptor 2B subunit gene (GRIN2B) were associated with TS in Chinese Han trios.

Methods: DNA samples collected from 261 TS nuclear families were genotyped by PCR and direct sequencing technology. Haplotype relative risk (HRR), transmission disequilibrium test (TDT) and Haplotype-based haplotype relative risk (HHRR) analyses were performed on the genotype data.

Results: We found an over-transmission of the A allele in rs1805476 and the T allele in rs1805502 from parents to their affected children, using the HRR (rs1805476: HRR=0.696, χ(2)=4.161, P=0.041, 95% CI: 0.491-0.986; rs1805502: HRR=0.697, χ(2)=3.954, P=0.047, 95% CI: 0.488-0.995). There was also strong evidence for a linkage between polymorphisms and TS using the TDT (rs1805476: TDT=5.447, df=1, P=0.024; rs1805502: TDT=5.233, df=1, P=0.027).

Limitations: The sample is small and the current population is just limited to the Chinese Han population.

Conclusions: These data support the hypothesis that GRIN2B might play a major role in the pathogenesis of TS in Chinese Han trios. However, these results need to be replicated using larger datasets collected from different populations.