Fengyuan Che1, Ying Zhang2, Guiju Wang3, Xueyuan Heng4, Shiguo Liu5, Yifeng Du6. 1. Departmen of Neurology, Provincial Hospital affiliated Shandong University, No. 44 wenhua west road, Jinan, Shandong 250012, PR China; Department of Neurology, Linyi People's Hospital, Shandong University No. 27 Jiefang Road, Linyi, Shandong 276003, PR China. 2. Child Healthcare Department, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China. 3. Child Healthcare Department, Rizhao people's Hospital, Shandong, PR China. 4. Department of Neurology, Linyi People's Hospital, Shandong University No. 27 Jiefang Road, Linyi, Shandong 276003, PR China. 5. Prenatal diagnosis center, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China. Electronic address: liushiguo2002@126.com. 6. Departmen of Neurology, Provincial Hospital affiliated Shandong University, No. 44 wenhua west road, Jinan, Shandong 250012, PR China. Electronic address: duyifengpmd2000@yahoo.com.cn.
Abstract
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.
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.
Authors: Olga V Kochetova; Diana S Avzaletdinova; Gulnaz F Korytina; Tatyana V Morugova; Olga E Mustafina Journal: Mol Biol Rep Date: 2020-02-10 Impact factor: 2.316
Authors: Sébastien Küry; Geeske M van Woerden; Thomas Besnard; Martina Proietti Onori; Xénia Latypova; Meghan C Towne; Megan T Cho; Trine E Prescott; Melissa A Ploeg; Stephan Sanders; Holly A F Stessman; Aurora Pujol; Ben Distel; Laurie A Robak; Jonathan A Bernstein; Anne-Sophie Denommé-Pichon; Gaëtan Lesca; Elizabeth A Sellars; Jonathan Berg; Wilfrid Carré; Øyvind Løvold Busk; Bregje W M van Bon; Jeff L Waugh; Matthew Deardorff; George E Hoganson; Katherine B Bosanko; Diana S Johnson; Tabib Dabir; Øystein Lunde Holla; Ajoy Sarkar; Kristian Tveten; Julitta de Bellescize; Geir J Braathen; Paulien A Terhal; Dorothy K Grange; Arie van Haeringen; Christina Lam; Ghayda Mirzaa; Jennifer Burton; Elizabeth J Bhoj; Jessica Douglas; Avni B Santani; Addie I Nesbitt; Katherine L Helbig; Marisa V Andrews; Amber Begtrup; Sha Tang; Koen L I van Gassen; Jane Juusola; Kimberly Foss; Gregory M Enns; Ute Moog; Katrin Hinderhofer; Nagarajan Paramasivam; Sharyn Lincoln; Brandon H Kusako; Pierre Lindenbaum; Eric Charpentier; Catherine B Nowak; Elouan Cherot; Thomas Simonet; Claudia A L Ruivenkamp; Sihoun Hahn; Catherine A Brownstein; Fan Xia; Sébastien Schmitt; Wallid Deb; Dominique Bonneau; Mathilde Nizon; Delphine Quinquis; Jamel Chelly; Gabrielle Rudolf; Damien Sanlaville; Philippe Parent; Brigitte Gilbert-Dussardier; Annick Toutain; Vernon R Sutton; Jenny Thies; Lisenka E L M Peart-Vissers; Pierre Boisseau; Marie Vincent; Andreas M Grabrucker; Christèle Dubourg; Wen-Hann Tan; Nienke E Verbeek; Martin Granzow; Gijs W E Santen; Jay Shendure; Bertrand Isidor; Laurent Pasquier; Richard Redon; Yaping Yang; Matthew W State; Tjitske Kleefstra; Benjamin Cogné; Slavé Petrovski; Kyle Retterer; Evan E Eichler; Jill A Rosenfeld; Pankaj B Agrawal; Stéphane Bézieau; Sylvie Odent; Ype Elgersma; Sandra Mercier Journal: Am J Hum Genet Date: 2017-11-02 Impact factor: 11.025