Polymorphism Of Schizophrenia Research Articles

Involvement of CXCL10 rs4256246, CXCR4 rs2228014, CCR2 rs1799864 and CXCL16 rs2277680 in the Predisposition to Schizophrenia.

Chemokine ligands and their receptors have acquired less attention than pro- and anti-inflammatory cytokines in schizophrenia (SCZ). Thus, we aimed to examine the impact of functional polymorphisms of the chemokine genes CXCL10, CXCL16, CXCR4, and CCR2 in the development of SCZ. Using PCR-RFLP, we analyzed the selected polymorphisms in a Tunisian cohort composed of 200 patients with SCZ and 200 healthy controls. Our preliminary data suggest that the minor allele A of CXCL10 rs4256246 is significantly associated with likelihood of SCZ (PAdjusted = 0.00002) and more precisely to paranoid patients with late-onset SCZ (PAdjusted = 0.0007). However, the mutated allele T of CXCR4 rs2228014 showed a significant protective impact against SCZ (PAdjusted = 0.000007) and especially to male sex (PAdjusted = 0.000003). This effect persists among the undifferentiated patients with early-onset SCZ (PAdjusted = 0.002). Following the stratified analyses, CCR2 rs1799864 and CXCL16 rs2277680 were significantly correlated with the clinical symptoms among disorganized patients. As regards haplotype analysis, we noted that GATG haplotype was associated with protection against SCZ (PAdjusted = 0.0087) but the AGCG haplotype was correlated with susceptibility to this disease (PAdjusted = 0.014). Our preliminary results suggested that CXCL10 rs4256246 enhanced susceptibility to SCZ, while CXCR4 rs2228014 seemed to be protective factor. Furthermore, we identified a substantial correlation between CCR2 rs1799864 and CXCL16 rs2277680 with the clinical signs of the disorder. To validate these results and clarify the functional significance of the targeted polymorphisms in SCZ, more independent research is needed.

The Relationship Between Sexual Dysfunctions With Disease Prolactin and Genetic Polymorphisms in Schizophrenia and Bipolar Disorder Patients Receiving Pharmacotherapy.

The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy. This study included 111 patients. The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS) were applied to the schizophrenia, and the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) to the bipolar patient group. The sociodemographic data form and the Arizona Sexual Experiences Scale (ASEX) were applied to both of the patient groups. Blood was drawn from all patients to evaluate the indicated gene polymorphisms and evaluate prolactin levels. SD was detected in 45.9% (N = 34) of the schizophrenia group, and 59.5% (N = 22) in the bipolar disorder group. SD was significantly higher in elderly patients and patients with a high smoking amount and low education levels. The eNOS -786T>C T allele frequency was found to be significantly higher in patients with SD. The logistic regression analysis determined that eNOS -786T>C CT and TT genotypes increased the risk of SD. In this study, the high rates of SD in patients with schizophrenia and bipolar disorder, and the presence of modifiable factors that influence the presence of SD, suggest that SD should be given more attention in these patient groups. On the other hand, the high rate of SD in patients with the eNOS -786T>C T allele indicates the importance of carrying out new studies investigating the factors affecting the enzyme activity in this genotype.There is a need for more studies on eNOS genotypes and enzyme activites in this area.

The relationship of the methylation status and polymorphism of glucocorticoid receptor gene (NR3C1) with attempted suicide or non-suicidal self-injury patients in schizophrenia.

We aim to investigate the methylation of NR3C1 gene promotor and NR3C1 BclI polymorphism in schizophrenia (SCZ) patients with attempted suicide or non-suicidal self-injury (NSSI). A sample of 112 patients with SCZ was included in the study. Structured Clinical Interview for Diagnostic and Statistical Manual-Fourth Edition Axis I Disorders was used to confirm the diagnosis according to The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria. The patients were evaluated by data forms that had sociodemographic, suicidal behavior, and NSSI information. Methylation-specific polymerase chain reaction (PCR) was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR restriction fragment length polymorphism. Our results revealed that although the NR3C1 gene methylation was not statistically significantly different, there was a significant difference in NR3C1 genotype distribution among the SCZ groups with and without attempted suicide. SCZ patients carrying the CC genotype had a lower risk of attempted suicide (Odds Ratio [OR]: 0.421; 95% Confidence Interval [CI]: 0.183-0.970; p = 0.040), while having the GG genotype in SCZ patients was associated with a higher risk of attempted suicide (OR: 3.785; 95% Cl: 1.107-12.945; p = 0.042). Additionally, due to NSSI in SCZ patients, there were no significant differences in NR3C1 gene methylation and NR3C1 genotype distribution among the groups. We propose that the NR3C1 BclI polymorphism may be associated with attempted suicide in Turkish patients diagnosed with SCZ.

Neurotrophin-3 gene polymorphism in schizophrenia and its relation with diseases severity and cognitive dysfunction.

Synaptic plasticity markers are known to alter in schizophrenia. The objective of the study was to investigate the genotype and allele frequency of neurotrophin-3 (NT-3) gene polymorphism (rs6489630, rs6332, and rs11063714) and plasma NT-3 levels in schizophrenia and their relation with cognitive status. The study was conducted on 216 Schizophrenia patients and 216 controls. Single-nucleotide polymorphism (SNP) of NT-3 and its plasma levels were assessed in both groups. Cognitive status was evaluated using Addenbrooke Cognitive examination-III scores. The rs6489630 polymorphism was found to be significantly associated with the severity of schizophrenia (P = 0.004). The CT genotype (P = 0.02, OR = 1.631 [1.10-2.43]) and minor allele T (P = 0.004, OR = 1.58 [1.16-2.16]) of rs6489630 conferred an increased susceptibility to develop schizophrenia. The rs6332 variant was found to affect cognitive status significantly in schizophrenia (P = 0.040), and memory dysfunction was seen in individuals with AG (P < 0.01) and AA variant (P = 0.03) of rs6332. We conclude that SNPs of NT-3 enhance the risk of schizophrenia and are related to cognitive dysfunction.

Research Progress of Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism in Schizophrenia

Schizophrenia is now considered to be a severe mental disorder caused by complex gene-environment interactions. Brain-derived neurotrophic factor (BDNF) is involved in the development, differentiation, and plasticity of neurons. The Val66Met polymorphism has been associated with impaired neurocognitive function in healthy adults and has been identified as a risk site for a range of neuropsychiatric disorders, including schizophrenia. In this paper, the relationship between BDNFVal66Met polymorphism and schizophrenia is reviewed.

Interleukin-1 receptor antagonist (IL-1RA) and interleukin-4 (IL-4) variable number of tandem repeat polymorphisms in schizophrenia and bipolar disorder: an association study in Turkish population

BackgroundPro-inflammatory/anti-inflammatory cytokine imbalance in cerebrospinal fluid or plasma of schizophrenia (SCZ) and bipolar disorder (BD) patients has been documented over the last decade. We aim to examine the interleukin-1 receptor antagonist (IL-1RA) and IL-4 variable number of tandem repeat (VNTR) polymorphisms in SCZ and BD patients by comparing them with healthy controls.MethodsTwo hundred and thirty-four unrelated patients (127 patients with SCZ, 107 patients with BD) and 204 healthy controls were included. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis. In addition, the polymerase chain reaction technique was used to investigate IL-1RA and IL-4 VNTR polymorphisms.ResultsOur results showed that the distributions of IL-1RA and IL-4 genotype and the allele frequencies of SCZ or BD patients were not significantly different from the healthy control group. IL-1RA allele 2 homozygous genotype and IL-1RA allele 2 frequencies were non-significantly higher among SCZ patients than in controls.ConclusionsOur study indicates that the IL-1RA and IL-4 VNTR polymorphisms are not considered risk factors for developing SCZ and BD among Turkish patients.

Molecular genetic study of clinical and cognitive features of schizophrenia: No associations with genes SOD2, GSTO1, NQO1

The main features of schizophrenia are characterized by three domains of symptoms, including positive symptoms, negative symptoms, and cognitive defi cits, the overlap of which forms a polymorphism of clinical manifestations. Previous molecular genetic studies have found signifi cant genetic overlaps between the cognitive abilities and the risk of schizophrenia developing. Recent evidence suggests that oxidative stress may play an important role in the pathophysiology of schizophrenia.Aim. The aim of the study was to investigate the associations of polymorphisms of genes encoding the antioxidant enzymes SOD2, GSTO1, and NQO1 with clinical polymorphism of schizophrenia and the severity of cognitive deficit.Material and Methods. A comprehensive examination of 457 patients with a diagnosis of schizophrenia was carried out. Out of the total group of examined patients, cognitive functions were assessed using the BACS scale in 150 schizophrenic patients. The control group comprised 135 healthy individuals with age and gender corresponding to patient group. Their cognitive function was assessed. Genotyping of SOD2 (rs4880), GSTO1 (rs4925), and NQO1 (rs1800566) was done by realtime PCR.Results. When analyzing the distribution of genotypes and alleles of polymorphic variants of genes encoding the antioxidant enzymes SOD2, GSTO1, and NQO1, no associations between the studied loci and schizophrenia in the Russian population of the Siberian region were revealed. Also, no associations were found with clinical polymorphism of disease (disease course type, leading symptoms (positive or negative), and age of disease onset). The cognitive abilities of schizophrenic patients and healthy individuals were diff erent as expected, but no associations with genetic characteristics were found.Conclusion. In this work, we obtained negative results in regard to associations of polymorphic variants of genes encoding the antioxidant enzymes SOD2 (rs4880), GSTO1 (rs4925), and NQO1 (rs1800566) with the development of schizophrenia in the Russian population in the Siberian region, as well as with the severity of cognitive defi cit. The genetic profi le for the studied loci did not aff ect the clinical manifestations of disease in the examined sample.

FOXP2 expression and gray matter density in the male brains of patients with schizophrenia

Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls. This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia.

Association of circulating BDNF levels with BDNF rs6265 polymorphism in schizophrenia

Schizophrenia is a severe neuropsychiatric disorder affecting 1% of the world population. Disturbances in neuronal development and synaptic connections are important factors in the pathogenesis of schizophrenia. Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays a critical role in the development of neurons. Among several polymorphisms reported in BDNF, the rs6265 polymorphism is known to be associated with many neuropsychiatric diseases. This study was aimed to determine the effect of BDNF rs6265 functional polymorphism on serum BDNF concentration in patients with schizophrenia. In total, 50 schizophrenia patients and 50 controls were recruited after obtaining written informed consent. Serum BDNF levels were estimated using the ELISA method and BDNF rs6265 polymorphism was genotyped using T-ARMS PCR. Serum BDNF levels were decreased significantly in schizophrenia patients when compared to the healthy controls (p < 0.0001). Further, the rs6265 polymorphism was also not associated with the schizophrenia (p = 0.41). Intragroup analysis between different genotypes revealed no association between the serum BDNF levels and rs6265 polymorphism. Our results suggest that the functional polymorphism rs6265 is not associated with serum BDNF levels, which is in line with previous findings, which indicates that serum BDNF levels depend more on diagnostic effect than genetic effect. Replication studies on a larger study population are needed.

Synonymous polymorphism rs201256011 in dopamine receptor type 2 gene is associated with schizophrenia and PANSS score in Pakistani population: A first report.

Variations of dopamine receptor type 2 (DRD2) are among the key factors involved in the pathology of schizophrenia. Presence of certain SNPs in DRD2 gene also amend patients' response to antipsychotics. Keeping in view the genetic diversity among populations and important role of DRD2 polymorphisms in schizophrenia, we aimed to study two of its SNPs rs1801028 and rs6277 in patients with schizophrenia from Pakistan. A total of 100 schizophrenia cases and 100 healthy controls were recruited. DNA was extracted from whole blood followed by PCR, Sanger sequencing and genotyping of two SNPs, that is, rs1801028 and rs6277. No association of rs1801028 and rs6277 was found with schizophrenia in Pakistani population (P>.05). Highlight of our study is the association of polymorphism rs201256011 with schizophrenia (P=.001), which is being reported for the first time. Significant association of rs201256011 was also found with Positive and Negative Syndrome Scale negative, cognitive and total score (P<.05). In conclusion, genetic variants rs1801028 and rs6277 of DRD2 are not associated with schizophrenia in Pakistani population. While, previously unreported polymorphism rs201256011 have shown significant association with schizophrenia and its severity. A large scale multicentre replication study is required to confirm the association of this SNP with schizophrenia.

An Analysis of Five TrkB Gene Polymorphisms in Schizophrenia and the Interaction of Its Haplotype with rs6265 BDNF Gene Polymorphism.

Aim The BDNF dysfunction in the schizophrenia has been soundly documented. The TrkB gene is a high-affinity receptor of the BDNF that is changed in schizophrenia and mood disorders. The study had two aims: first, to identify whether the five nucleotide polymorphisms (SNPs) in TrkB gene are associated with a diagnosis of schizophrenia; and the latter, if any association exists between the TrkB SNPs and psychopathology, suicide attempts, and family history of schizophrenia in a Caucasian population. Methods Case-control study (401 patients and 657 healthy controls) was used to examine a predisposition for schizophrenia. The tests for psychopathology, suicide attempts, and family history of schizophrenia were conducted only in patient group. The severity of the schizophrenia was measured using the five-factor model of the PANSS. In addition, the haplotype analysis for both the separate for SNPs of TrkB gene and in combination with the rs6265 SNP BDNF gene was conducted. Results Our case-control study revealed that the genetic variants of rs10868235 (T/T polymorphic genotype) and rs1387923 (G/G polymorphic genotype) of the TrkB gene were associated with a higher risk of developing schizophrenia in men. However, the A/A wild genotype of rs1387923 was connected with a lower risk for both the development of and the family manifestation of schizophrenia in men. The G polymorphic allele of rs1565445 was associated with an increased risk of suicide in schizophrenia. The tested SNPs of the TrkB gene did not modulate the psychopathology of schizophrenia. The haplotype that was built with five SNPs in the TrkB gene was protective for men, but after joining the rs6265 SNP of the BDNF gene, a haplotype that was protective for women was created.

Association of MIF and MBL2 gene polymorphisms with attempted suicide in patients diagnosed with schizophrenia or bipolar disorder

The aim of this study to investigate the genetic polymorphisms in macrophage inhibitory factor (MIF) and mannose-binding lectin 2 (MBL2) gene in schizophrenia (SCZ) or bipolar disorder (BD) patients with attempted suicide by comparing with a non-attempted SCZ or BD patients and healthy controls. A sample of 108 patients with SCZ, 100 patients with BD and 100 healthy volunteers were included in the study. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The patients were evaluated by data forms that included sociodemographic, suicidal behavior and symptom severity information. PCR-RFLP was used to determine MIF and MBL2 gene polymorphisms from DNA material. Our results demonstrated that the distributions of MBL2 genotype (AA, AB, BB), combined genotype (AA, AB/BB) and the allele frequencies (A, B) of attempted suicide patients in SCZ were significantly different from the non-attempted SCZ patients. The distributions of the MBL2 genotype of attempted suicide patients in SCZ were significantly different from the control group. The distributions of MIF genotype (GG, GC, CC), combined genotype (GG, GC/CC) and the allele frequencies (G, C) of attempted suicide patients in BD were significantly different from the non-attempted BD patients or control group. In summary MBL2 gene polymorphism may be associated with attempted suicide in SCZ and MIF gene polymorphism might be associated with attempted suicide in BD. However, further studies with other gene variants in different ethnic populations are needed to address the exact role of these polymorphisms in SCZ or BD.

Study of the association between DRD2 Gene Ser311Cys and GSTM1 Gene Polymorphism in Schizophrenia

Introduction: Schizophrenia is a mental disorder affecting 1% of the world's population. Two of genes have been recognized to be involved in development of this disease: DRD2 and GSTM1. Methods: This case-control study included 100 patients suffering from schizophrenia who referred to Yazd Neuropsychiatry Hospital. Also, 100 healthy patients without schizophrenia were selected as the control group. After DNA extraction, it was genotyped 100 schizophrenic and 100 healthy controls by use of restricted fragment of length polymorphism (RFLP) for Ser311Cys polymorphism and multiplex PCR for GSTM1. After performing relevant experiments and gaining some results, statistical analysis was performed using SPSS software16. In this study, Chi-square and logistic regression tests were used to investigate the relation between genotype of polymorphism and schizophrenia. Results: Data analysis showed that frequency distribution of Ser311Cys polymorphism genotypes between the patients and healthy participants was not significant (P: 0.121). Also, for GSTM1, there was no association between the polymorphism and schizophrenia. In general, the frequency distribution of the deleting gene between the patients and the control group was not significant (P= 0.089). And this polymorphism was significantly associated with symptoms (P = 0.012). Conclusion: The results of this study show that Ser311Cys polymorphism and GSTM1 polymorphism is not common among the studied patients, therefore it indicates its non-effectiveness in the study population. However, because the study population is not representative of the entire Iranian population, further studies with larger population are needed.

Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes

BackgroundMethylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. ResultsSchizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. ConclusionsThis is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia.

Replication of GWAS identified miR-137 and its target gene polymorphisms in Schizophrenia of South Indian population and meta-analysis with Psychiatric Genomics Consortium

Schizophrenia is a complex psychiatric disorder involving multiple genes each contributing a small risk. Genome-wide association studies (GWASs) have identified hundreds of risk loci for schizophrenia including miR-137, a miRNA shown to be involved in neuronal development. Several genes regulated by miR-137 were also reported as top risk genes associated with schizophrenia and has been hypothesised that the dysregulation of miR-137 and its target could be involved in the aetiology of schizophrenia. Here, we replicated the four European GWAS hits, miR-137-rs1625579 and three of its validated target gene loci SNPs (ZNF804a-rs1344706, CACNA1C-rs4765905 and TCF4-rs9960767) by genotyping in 2074 samples (schizophrenia cases-1005; controls-1069) from South Indian Population. In this study, only the CACNA1C rs4765905 showed a significant association (OR=1.24, p=0.006). Three SNPs (rs1625579, rs1344706 and rs4765905) showed a consistent direction of effect with previous studies and the polygenic risk score constructed using the weighted sum of these three SNPs showed a significant association with Schizophrenia in this population (OR=3.78, p=0.005). Further, we carried out meta-analysis combining our results with the Psychiatric Genomics Consortium (PGC2) data and observed a considerable increase in GWAS significance.

Analyzing a single nucleotide polymorphism in schizophrenia: a meta-analysis approach.

BackgroundSchizophrenia is a severe mental disorder affecting >21 million people worldwide. Some genetic studies reported that single nucleotide polymorphism (SNP) involving variant rs1344706 from the ZNF804A gene in human beings is associated with the risk of schizophrenia in several populations. Similar results tend to conflict with other reports in literature, indicating that no true significant association exists between rs1344706 and schizophrenia. We seek to determine the level of association of this SNP with schizophrenia in the Asian population using more recent genome-wide association study (GWAS) datasets.MethodsApplying a computational approach with inclusion of more recent GWAS datasets, we conducted a meta-analysis to examine the level of association of SNP rs1344706 and the risk of schizophrenia disorder among the Asian population constituting Chinese, Indonesians, Japanese, Kazakhs and Singaporeans. For a total of 21 genetic studies, including a total of 28,842 cases and 35,630 controls, regression analysis, publication bias, Cochran’s Q and I2 tests were performed. The DerSimonian and Laird random-effects model was used to assess the association of the genetic variant to schizophrenia. Leave-one-out sensitivity analysis was also conducted to determine the influence of each study on the final outcome of the association study.ResultsOur summarized analysis for Asian population revealed a pooled odds ratio of 1.06, 95% confidence interval of 1.01–1.11 and two-tailed P-value of 0.0228. Our test for heterogeneity showed the presence of large heterogeneity (I2=53.44%, P =0.00207) and Egger’s regression test (P =0.8763) and Begg’s test (P =0.8347), indicating no presence of publication bias among our selected studies. In our sensitivity analysis, 10 different studies comprising of ~50% of the entire study had an impact on our final results as each leave-one-out test became insignificant. Our result suggests that genetic variant rs1344706 might be associated with the development of schizophrenia in Asians.

Family-based association study of interleukin 10 (IL10) and interleukin 10 receptor alpha (IL10RA) functional polymorphisms in schizophrenia in Polish population

Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. Interleukin-10 (IL10) and it's receptor IL10RA may play an important role for immunological aspects in etiologies of major psychiatric disorders including schizophrenia. The aim of this study was to perform a transmission disequilibrium test (TDT) on a group of 146 schizophrenia trios from the Polish population. Functional polymorphisms from IL10 (rs1800872, rs1800871, rs1800896, rs1800890, and rs6676671) and IL10RA (rs3135932 and rs2229113) genes were analyzed. A lack of association with schizophrenia was detected for IL10 and IL10RA single polymorphisms and haplotypes

The Role of a Catechol-O-Methyltransferase (COMT) Val158Met Genetic Polymorphism in Schizophrenia: A Systematic Review and Updated Meta-analysis on 32,816 Subjects.

An association between a catechol-O-methyltransferase (COMT) Val156Met (rs4680) polymorphism and schizophrenia has been reported in the literature, although no conclusive outcomes have been attained. The aim of this study was to evaluate the association of the COMT Val108/158Met polymorphism with schizophrenia in a systematic review and meta-analysis. We performed a keyword search on PubMed and EBSCO databases. All English language case-control studies published up to April 2015 were selected. A total of 67 studies were selected for inclusion. The genotype distribution of subjects with schizophrenia was compared with healthy control subjects, using allelic, additive, dominant and recessive models. The pooled results from the meta-analysis (15,565 cases and 17,251 healthy subjects) after the elimination of heterogeneity showed an association between COMT Val108/158Met and schizophrenia [recessive model: OR 1.08 CI 95% (1.01-1.15)]. We conducted subgroup analyses according to ethnicity. An association was observed in our Caucasian population in the additive model [OR 1.21 CI 95% (1.06-1.37)] and in the recessive model [OR 1.21 CI 95% (1.11-1.32)], but not in the allelic or dominant models. However, when we analysed our Asian population after the elimination of heterogeneity, no evidence of a significant association was found in any of the genetic models. Our analyses indicate that there is an association between COMT Val108/158Met and schizophrenia in the general population. Furthermore, in Caucasian populations, this risk could be increased.

Family association study of Transforming Growth Factor Beta1 gene polymorphisms in schizophrenia.

Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. An etiopathological role for immunologic abnormalities in schizophrenia was hypothesized. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, antiinflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Transforming Growth Factor Beta 1 (TGFB1) signaling is critical for many biological processes, including proliferation, development, differentiation and regeneration. Multiple members of the TGFB1 superfamily play a role in the developing nervous system and are regulated by neuronal activity. We conducted family-based study to assess whether TGFB1 gene is associated with susceptibility to schizophrenia in Polish population. Two functional polymorphisms: rs1800469 (C-509T) and rs1800470 (T869C) of TGFB1 gene were analyzed within a group of 147 trios (patients diagnosed with schizophrenia and their healthy parents) using Transmission Disequilibrium Test (TDT). No association of these polymorphisms with schizophrenia was found in Polish population. Further studies on larger groups along with correlation with circulating protein levels are needed.

Dopamine D1 receptor (DRD1) 5′ region haplotypes significantly affect transcriptional activity in vitro

The role of dopamine D1 receptor (DRD1) gene promoter polymorphisms in schizophrenia remains controversial. We aimed to characterize the polymorphisms in the promoter region because little is known about the extent of variance in this region and potential roles in gene transcription activity. In a previous case-control study, we amplified and genotyped the polymorphisms of DRD1 gene. According to its haplotype estimation, we identified eight SNPs and confirmed ten different haplotypes by cloning and sequencing the fragment spanning −1990 to +10. The promoter activity of these haplotypes was analyzed using dual luciferase assays in SH-SY5Y and HEK293 cells. Compared with the reference haplotype, the constructed haplotypes containing different variation sites could significantly alter the luciferase activity. Additionally, the prediction of the transcription factor binding sites was performed. Our examination could provide the informative reference for the role of DRD1 gene promoter in schizophrenia.