Lim, Chor Hong (2016) Bipolar disorder: Microrna profiling and genetics comparison with schizophrenia in a Malaysian population / Lim Chor Hong. Masters thesis, University of Malaya.
Abstract
Recent studies have shown that bipolar disorder (BPD) and schizophrenia (SZ) share some common genetic risk factors. This study aimed to examine the association between candidate single nucleotide polymorphisms (SNPs) identified from genomewide association studies (GWAS) and risk of BPD and SZ. A total of 715 patients (244 BPD and 471 SZ) and 593 controls were genotyped using the Sequenom MassARRAY platform. We showed a positive association between LMAN2L (rs6746896) and risk of both BPD and SZ in a pooled population (P-value=0.001 and 0.009, respectively). Following stratification by ethnicity, variants of the ANK3 gene (rs1938516 and rs10994336) were found to be associated with BPD in Malays (P-value=0.001 and 0.006, respectively). Furthermore, an association exists between another variant of LMAN2L (rs2271893) and SZ in the Malay and Indian ethnic groups (P-value=0.003 and 0.002, respectively). Gene-gene interaction analysis revealed a significant interaction between the ANK3 and LMAN2L genes (empirical P=0.0107). Significant differences were shown between patients and controls for two haplotype frequencies of LMAN2L: GA (P=0.015 and P=0.010, for BPD and SZ, respectively) and GG (P=0.013 for BPD). Our study showed a significant association between LMAN2L and risk of both BPD and SZ. Although major progress has been achieved in terms of research and development, there stills exists gap in the knowledge of molecular mechanisms underlying bipolar disorder (BPD) and action pathway of atypical antipsychotics. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity. This study aimed to examine the changes in miRNA expression in the blood of 14 bipolar mania patients following 12 weeks of treatment with asenapine and risperidone using miRNA microarray. A total of 24 miRNAs were differentially expressed after treatment in asenapine group, 22 of which were significantly up-regulated and the other two were iv significantly down-regulated. However, all three differentially expressed miRNAs in the risperidone group were down-regulated. MiRNA target gene prediction and gene ontology analysis revealed significant enrichment for pathways associated with immune system response and regulation of programmed cell death and transcription. Our results show that miRNAs were involved in the pathway mechanism of both antipsychotics.
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