Abstract
Both genome wide association study (GWAS) and biochemical studies of Caucasian populations indicate a robust association between the miR-137 genetic variant rs1625579 and schizophrenia, but inconsistent results have been reported. To assay the association between this variant and schizophrenia, we genotyped 611 schizophrenic patients from Southern Chinese Han population for the risk single nucleotide polymorphism (SNP) rs1625579 using the SNaPshot technique and compared the clinical profiles of different genotypes. Additionally, a meta-analysis was performed using the combined sample groups from five case-control publications and the present study. Both the genotype and allele distributions of the rs1625579 SNP were significantly different between patients and controls (P = 0.036 and 0.026, SNP). TT genotype carriers showed slightly lower Brief Assessment of Cognition in Schizophrenia- (BACS-) derived working memory performance than G carriers (15.58 ± 9.56 versus 19.71 ± 8.18, P = 0.045). In the meta-analysis, we observed a significant association between rs1625579 and schizophrenia under different genetic models (all P < 0.05). The results of our study and meta-analysis provide convincing evidence that rs1625579 is significantly associated with schizophrenia. Furthermore, the miR-137 polymorphism influences the working memory performance of schizophrenic patients in a Chinese Han population.
Highlights
MiRNAs are small, noncoding RNAs that regulate gene expression posttranscriptionally [1]
MiR-137 is a candidate gene for schizophrenia susceptibility and was identified by a recent mega-genome wide association study (GWAS) analysis in the sample of European ancestry conducted by the Psychiatric GWAS Consortium (PGC) [9], where a polymorphism located in the primary transcript of hsa-miR-137 had the strongest genetic signal associated with schizophrenia
Four other schizophrenia associated genes (TCF4, CACNA1C, CSMD1, and C10orf26) identified in that study contain predicted miR-137 binding sites [10], suggesting that the interplay between miR-137 and its target genes could be involved in the etiology of schizophrenia [11,12,13]
Summary
MiRNAs are small, noncoding RNAs that regulate gene expression posttranscriptionally [1]. Over half of the miRNAs identified far are highly or exclusively expressed in the brain, where they act as integral regulators of neuronal genes involved in the function, plasticity, and development of the brain [2, 3]. Hsa-miR-137, as a brain-enriched micro-RNA, has important roles during neurogenesis, including the proliferation and differentiation of neural stem cells, the regulation of dendritic morphogenesis, and synaptic plasticity [2, 7, 8]. MiR-137 is a candidate gene for schizophrenia susceptibility and was identified by a recent mega-GWAS analysis in the sample of European ancestry conducted by the Psychiatric GWAS Consortium (PGC) [9], where a polymorphism (rs1625579) located in the primary transcript of hsa-miR-137 had the strongest genetic signal associated with schizophrenia. Four other schizophrenia associated genes (TCF4, CACNA1C, CSMD1, and C10orf26) identified in that study contain predicted miR-137 binding sites [10], suggesting that the interplay between miR-137 and its target genes could be involved in the etiology of schizophrenia [11,12,13].
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