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Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population.

Zhang Y, Fan M, Wang Q, He G, Fu Y, Li H, Yu S - Sci Rep (2015)

Bottom Line: Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele.MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model.These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.

ABSTRACT
Disturbances in glutamate signaling caused by disruption of N-methyl-D-aspartate-type glutamate receptor (NMDAR) have been implicated in schizophrenia. Findings suggested that miR-219, miR-132 and miR-107 could involve in NMDAR signaling by influencing the expression of pathway genes or the signaling transmission and single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA target sites could result in their functional changes. Therefore, we hypothesized that SNPs in miRNAs and/or their target sites were associated with schizophrenia. 3 SNPs in hsa-pri-miR-219/132/107 and 6 SNPs in 3'UTRs of GRIN2A/2B/3A and CAMK2G were selected and genotyped in a case-control study of 1041 schizophrenia cases and 953 healthy controls in Chinese Han population. In the present study, GRIN2B rs890 showed significant associations with schizophrenia. Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele. MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model. These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.

No MeSH data available.


Related in: MedlinePlus

Possible roles of miRNAs in NMDA signaling pathway associated with SCZ.
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f1: Possible roles of miRNAs in NMDA signaling pathway associated with SCZ.

Mentions: Disturbances in glutamatergic neurotransmission, particularly caused by dysfunction or dysregulation of N-methyl-D-aspartate-type glutamate receptor (NMDAR) is regarded as the final common pathway on the road to SCZ7. Several findings suggested that miR-219, miR-132, and miR-107 had important roles in regulating NMDAR-induced calcium signaling pathway6 (Fig. 1).


Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population.

Zhang Y, Fan M, Wang Q, He G, Fu Y, Li H, Yu S - Sci Rep (2015)

Possible roles of miRNAs in NMDA signaling pathway associated with SCZ.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530343&req=5

f1: Possible roles of miRNAs in NMDA signaling pathway associated with SCZ.
Mentions: Disturbances in glutamatergic neurotransmission, particularly caused by dysfunction or dysregulation of N-methyl-D-aspartate-type glutamate receptor (NMDAR) is regarded as the final common pathway on the road to SCZ7. Several findings suggested that miR-219, miR-132, and miR-107 had important roles in regulating NMDAR-induced calcium signaling pathway6 (Fig. 1).

Bottom Line: Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele.MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model.These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.

ABSTRACT
Disturbances in glutamate signaling caused by disruption of N-methyl-D-aspartate-type glutamate receptor (NMDAR) have been implicated in schizophrenia. Findings suggested that miR-219, miR-132 and miR-107 could involve in NMDAR signaling by influencing the expression of pathway genes or the signaling transmission and single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA target sites could result in their functional changes. Therefore, we hypothesized that SNPs in miRNAs and/or their target sites were associated with schizophrenia. 3 SNPs in hsa-pri-miR-219/132/107 and 6 SNPs in 3'UTRs of GRIN2A/2B/3A and CAMK2G were selected and genotyped in a case-control study of 1041 schizophrenia cases and 953 healthy controls in Chinese Han population. In the present study, GRIN2B rs890 showed significant associations with schizophrenia. Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele. MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model. These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.

No MeSH data available.


Related in: MedlinePlus