Dataset Information

Quantitative DNA Methylation Analysis of DLGAP2 Gene using Pyrosequencing in Schizophrenia with Tardive Dyskinesia: A Linear Mixed Model Approach.

ABSTRACT: Tardive dyskinesia (TD) is a side effect of antipsychotic medications used to treat schizophrenia (SCZ) and other mental health disorders. No study has previously used pyrosequencing to quantify DNA methylation levels of the DLGAP2 gene; while the quantitative methylation levels among CpG sites within a gene may be correlated. To deal with the correlated measures among three CpG sites within the DLGAP2 gene, this study analyzed DNA methylation levels of the DLGAP2 gene using a linear mixed model (LMM) in a Chinese sample consisting of 35 SCZ patients with TD, 35 SCZ without TD (NTD) and 34 healthy controls (HCs) collected in Beijing, China. The initial analysis using the non-parametric Kruskal-Wallis test revealed that three groups (TD, NTD and HC) had significant differences in DNA methylation level for CpG site 2 (p?=?0.0119). Furthermore, the average methylation levels among the three CpG sites showed strong correlations (all p values?

SUBMITTER: Li Y

PROVIDER: S-EPMC6269460 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Quantitative DNA Methylation Analysis of DLGAP2 Gene using Pyrosequencing in Schizophrenia with Tardive Dyskinesia: A Linear Mixed Model Approach.

Li Yanli Y Wang Kesheng K Zhang Ping P Huang Junchao J An Huimei H Wang Nianyang N De Yang Fu F Wang Zhiren Z Tan Shuping S Chen Song S Tan Yunlong Y

Scientific reports 20181130 1

Tardive dyskinesia (TD) is a side effect of antipsychotic medications used to treat schizophrenia (SCZ) and other mental health disorders. No study has previously used pyrosequencing to quantify DNA methylation levels of the DLGAP2 gene; while the quantitative methylation levels among CpG sites within a gene may be correlated. To deal with the correlated measures among three CpG sites within the DLGAP2 gene, this study analyzed DNA methylation levels of the DLGAP2 gene using a linear mixed model ...[more]

PMID: 30504779

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Project description:BackgroundTardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia.MethodsA set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4.ResultsStatistically significant associations of rs1928040 of HTR2A gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results.ConclusionWe found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest that rs1801412 is directly or indirectly linked to the functioning of HTR2C. Further study of variants of the HTR2C gene in a larger group of male patients who were not using HTR2C antagonists is necessary in order to verify a possible functional role of this receptor.

Project description:OBJECTIVE:We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. METHOD:This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with ?(2) tests. Data were collected from January 2001 to December 2004. RESULTS:Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (?(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ? 50% decrease in AIMS score, and 7% showed a ? 50% increase in AIMS score. CONCLUSIONS:Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00014001.

Dataset Information

Quantitative DNA Methylation Analysis of DLGAP2 Gene using Pyrosequencing in Schizophrenia with Tardive Dyskinesia: A Linear Mixed Model Approach.

Publications

Quantitative DNA Methylation Analysis of DLGAP2 Gene using Pyrosequencing in Schizophrenia with Tardive Dyskinesia: A Linear Mixed Model Approach.

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