Subject(s)
Schizophrenia/genetics , Case-Control Studies , Humans , Malaysia , Pedigree , Proto-Oncogene Proteins c-aktABSTRACT
Transcription factor 4 (TCF4) gene plays an important role in nervous system development and it always associated with the risk of schizophrenia. Since miRNAs regulate targetgenes by binding to 3'UTRs of target mRNAs, the functional variants located in 3'UTR of TCF4 are highly suggested to affect the gene expressions in schizophrenia. To test the hypothesis regarding the effects of the variants located in 3'UTR of TCF4, we conducted an in silico analysis to identify the functional variants and their predicted functions. In this study, we sequenced the 3'UTR of TCF4 in 13 multiplex schizophrenia families and 14 control families. We found two functional variants carried by three unrelated patients. We determined that the C allele of rs1272363 and the TC insert of rs373174214 might suppress post- transcriptional expression. Secondly, we cloned the region that flanked these two variants into a dual luciferase reporter system and compared the luciferase activities between the pmirGLO-TCF4 (control), pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263. Both pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263 caused lower reporter gene activities, as compared to the control. However, only the C allele of rs1272363 reduced the luciferase activity significantly (p = 0.0231). Our results suggested that rs1273263 is a potential regulator of TCF4 expression, and might be associated with schizophrenia.
Subject(s)
3' Untranslated Regions/genetics , Gene Expression Regulation/genetics , Schizophrenia/genetics , Transcription Factor 4/genetics , Adult , Cell Line, Tumor , Female , Humans , Male , MicroRNAs/metabolism , Pedigree , Polymorphism, Single Nucleotide , RNA, Messenger/metabolism , SiblingsABSTRACT
BACKGROUND: Age at onset (AAO) is a known prognostic indicator for schizophrenia and is hypothesized to correlate with cognition and symptom severity. TCF4 and AKT1 are schizophrenia risk genes involved in cognitive functions. The current study examined the interactive effects of TCF4 and AKT1 variants with gender, family history of psychiatric disorders and ethnicity on the AAO of schizophrenia. METHODS: This study consisted of 322 patients with schizophrenia meeting the DSM-IV criteria. Six single nucleotide polymorphisms (SNPs) of TCF4 (rs12966547, rs8766, rs2958182, rs9960767, rs10401120 and rs17512836) and seven AKT1 SNPs (rs2498804, rs3803304, rs2494732, rs3730358, rs1130214, rs2498784 and rs3803300) were genotyped using the TaqMan® SNP genotyping-based assays method. The relationship of AAO with each variant was investigated using analyses of covariance. RESULTS: Among the TCF4 variants, rs12966547 (p = 0.024) and rs8766 (p = 0.021) were significantly associated with earlier AAO. We found a lower average AAO in patients with the AA genotype of rs12966547, while the CT genotype of rs8766 was demonstrated to have a protective effect on AAO. For rs8766, there was significant gene × gender interaction (p = 0.012) in influencing AAO. However, these results were not significant after false discovery rate correction. Significant gene × ethnicity interactions were observed to influence AAO (p < 0.05). The Kaplan-Meier curve of the minor AA genotype of rs12966547 displayed a significant trend (p = 0.008) for onset after 19 years of age. Similarly, the minor CC genotype of rs8766 showed a significantly (p = 0.034) lower AAO compared to the TT genotype. CONCLUSION: Our analyses suggest that individual risk genotypes may influence the risk of schizophrenia in an age-specific manner.
Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Ethnicity/genetics , Proto-Oncogene Proteins c-akt/genetics , Schizophrenia/genetics , Transcription Factors/genetics , Adult , Age of Onset , Asian People/genetics , Female , Genotype , Humans , Malaysia , Male , Middle Aged , Polymorphism, Single Nucleotide , Schizophrenia/ethnology , Sex Factors , Transcription Factor 4 , White People/geneticsABSTRACT
We aim to replicate AKT1 gene variants studies using Malaysian samples. Seven AKT1 single nucleotide polymorphisms (SNPs) were studied in 417 patients and 429 controls. Haplotype showed significant association (p=0.036) with schizophrenia, especially in Malays and Indians. Meta-analysis of rs2494732 showed significant association worldwide (p=0.018) and in Asians (p=0.023).
Subject(s)
Proto-Oncogene Proteins c-akt/genetics , Schizophrenia/genetics , Adult , Female , Genetic Association Studies , Genotype , Humans , Malaysia/epidemiology , Malaysia/ethnology , Male , Middle Aged , Polymorphism, Single Nucleotide , Reference Values , Schizophrenia/ethnology , Young AdultABSTRACT
Neuregulin-1 is widely investigated due to its hypothesised association with schizophrenia. Single-nucleotide polymorphisms rs764059, rs2954041 and rs3924999 were investigated (417 patients with schizophrenia and 429 controls). We failed to demonstrate a significant association between rs2954041 and rs3924999 with schizophrenia in the three ethnic groups studied (Malay, Chinese, and Indian), while rs764059 was found to be monomorphic.
Subject(s)
Genetic Predisposition to Disease/genetics , Neuregulin-1/genetics , Schizophrenia/genetics , Adult , Asian People/genetics , Case-Control Studies , Female , Humans , Male , Polymorphism, Single Nucleotide , White People/geneticsABSTRACT
The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.
Subject(s)
Congresses as Topic , Schizophrenia , Humans , International Agencies , Italy , Schizophrenia/diagnosis , Schizophrenia/therapy , Societies, MedicalABSTRACT
Free radicals are produced as part of the body immune response triggered by exogenous oxidants. In excess, they impair antioxidant defence system and cause oxidative stress. Antioxidants are hypothesised as antidotes to counteract oxidative stress and improve immune function. Carotenoids serve as a reliable indicator of overall antioxidant level in humans. This study investigated the possible relationship of carotenoid antioxidant levels in schizophrenia. A total of 351 schizophrenic subjects from Hospital Bahagia Ulu Kinta, Malaysia and 247 healthy controls were recruited. Subjects' skin carotenoid levels were measured using a non-invasive technique, Raman spectroscopy. The results showed significant (P<0.01) reduction of carotenoid level in patient compared to healthy controls, suggesting higher levels of oxidative stress in schizophrenia. Comparison between gender, age, subtypes, antipsychotic drug treatments, and duration of illness was investigated, but none was significantly associated with carotenoid score. Antipsychotics were suggested to be the possible causes of reduced antioxidant level in schizophrenia.
