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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

The locations of 3 SNPs in the pri-miRNA transcripts.The locations of SNPs in pri-miRNAs are depicted on black line at the upstream (negative base count, ‘–’) or downstream (positive base count, ‘+’) of the pre-miRNA. The figure is not drawn to scale.
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f2: The locations of 3 SNPs in the pri-miRNA transcripts.The locations of SNPs in pri-miRNAs are depicted on black line at the upstream (negative base count, ‘–’) or downstream (positive base count, ‘+’) of the pre-miRNA. The figure is not drawn to scale.

Mentions: We selected 3 SNPs (rs107822, rs3803808, rs2296616) within +/−500 bp of hsa-pre-miR-219, hsa-pre-miR-132 and hsa-pre-miR-107 transcripts and 6 SNPs(rs1420040, rs1805502, rs890, rs16920487, rs12342026, rs2306327) in 3′UTR of NMDAR signaling pathway genes (GRIN1, GRIN2A, GRIN2B, GRIN3A and CAMK2G) from hapmap database (release #24) in Chinese Han population (minor allele frequency, MAF ≥ 0.05). According to the PolymiRTS Database 3.0 (a database of naturally occurring DNA variations in miRNA seed regions and miRNA target sites, http://compbio.uthsc.edu/miRSNP/home.php) and the patrocles (a database of polymorphic miRNA-target interation, http://www.patrocles.org/). rs1420040, rs890, rs16920487, rs12342026, rs2306327 were in the putative miRNA target sites. There was no SNPs in GRIN1 which meet our screening requirements. The locations of SNPs in the pri-miRNA were showed in Fig. 2. The information of SNPs in 3′UTR were showed in Table 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)

The locations of 3 SNPs in the pri-miRNA transcripts.The locations of SNPs in pri-miRNAs are depicted on black line at the upstream (negative base count, ‘–’) or downstream (positive base count, ‘+’) of the pre-miRNA. The figure is not drawn to scale.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: The locations of 3 SNPs in the pri-miRNA transcripts.The locations of SNPs in pri-miRNAs are depicted on black line at the upstream (negative base count, ‘–’) or downstream (positive base count, ‘+’) of the pre-miRNA. The figure is not drawn to scale.
Mentions: We selected 3 SNPs (rs107822, rs3803808, rs2296616) within +/−500 bp of hsa-pre-miR-219, hsa-pre-miR-132 and hsa-pre-miR-107 transcripts and 6 SNPs(rs1420040, rs1805502, rs890, rs16920487, rs12342026, rs2306327) in 3′UTR of NMDAR signaling pathway genes (GRIN1, GRIN2A, GRIN2B, GRIN3A and CAMK2G) from hapmap database (release #24) in Chinese Han population (minor allele frequency, MAF ≥ 0.05). According to the PolymiRTS Database 3.0 (a database of naturally occurring DNA variations in miRNA seed regions and miRNA target sites, http://compbio.uthsc.edu/miRSNP/home.php) and the patrocles (a database of polymorphic miRNA-target interation, http://www.patrocles.org/). rs1420040, rs890, rs16920487, rs12342026, rs2306327 were in the putative miRNA target sites. There was no SNPs in GRIN1 which meet our screening requirements. The locations of SNPs in the pri-miRNA were showed in Fig. 2. The information of SNPs in 3′UTR were showed in Table 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