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Association between the IL10 rs1800896 Polymorphism and Tardive Dyskinesia in Schizophrenia.

ABSTRACT: OBJECTIVE:Interleukin-10 (IL-10) is a major immunoregulatory cytokine and its gene plays a fundamental role in anti-inflammatory and immunosuppressive activity. This study aimed to examine the association between the IL10 gene promoter -1082G/A polymorphism (rs1800896) and tardive dyskinesia (TD) in schizophrenia. METHODS:Two hundred and eighty unrelated Korean schizophrenic patients participated in this study (105 TD and 175 non-TD patients). TD was diagnosed using the Research Diagnostic Criteria for TD and Abnormal Involuntary Movement Scale (AIMS). Genotyping was performed by RT-PCR and high-resolution melting curve analysis. RESULTS:The distributions of genotypic frequencies did not differ between patients with and without TD (?2=4.33, p=0.115). However, allelic frequencies of the two groups were different (?2=4.45, p=0.035); the A allele frequency was higher in TD. The total AIMS scores of the three genotypes were not different (F=1.33, p=0.266). However, the total AIMS scores of the A allele carrier and the A allele non-carrier were significantly different (t=5.79, p<0.001). Logistic regression analaysis showed that IL10 -1082G/A genotype significantly predicts presence of TD (p=0.045) after adjusting for covariates such as age and treatment duration. CONCLUSION:This finding suggests that the A allele of rs1800896 may be associated with TD development following a low IL-10 function.

SUBMITTER: Choi KY

PROVIDER: S-EPMC7596282 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Association between the IL10 rs1800896 Polymorphism and Tardive Dyskinesia in Schizophrenia.

Choi Kwang-Yeon KY Choo Jeong Min JM Lee Youn-Jung YJ Lee Yujin Y Cho Chul-Hyun CH Kim Seung-Hyun SH Lee Heon-Jeong HJ

Psychiatry investigation 20201016 10

<h4>Objective</h4>Interleukin-10 (IL-10) is a major immunoregulatory cytokine and its gene plays a fundamental role in anti-inflammatory and immunosuppressive activity. This study aimed to examine the association between the IL10 gene promoter -1082G/A polymorphism (rs1800896) and tardive dyskinesia (TD) in schizophrenia.<h4>Methods</h4>Two hundred and eighty unrelated Korean schizophrenic patients participated in this study (105 TD and 175 non-TD patients). TD was diagnosed using the Research D ...[more]

PMID: 33059393

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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:BackgroundDopamine-?-hydroxylase (DBH, EC 1.14.17.1), which converts dopamine to norepinephrine, is a candidate gene in neuropsychiatric diseases.AimTo assess the effect of regulatory variants in DBH on schizophrenia and its endophenotypes -cognition and tardive dyskinesia.MethodsWe tested association of functional variants 19bp Ins/Del, rs1989787 and rs1611115 in DBH with i) schizophrenia (1236 cases, 1136 controls), ii) tardive dyskinesia (83 positive, 162 negative) and iii) performance functions of cognition (357 cases, 306 controls) estimated by the Penn Computerized Neurocognitive Battery.ResultsA modest haplotypic (Ins-C; 19bp Ins/Del - rs1989787 C>T; p=0.04) association was observed with schizophrenia. We observed ~39% reduction in activity of 19bp Del allele on luciferase assay. Analysis of covariance revealed interactions of tardive dyskinesia status and: i) 19bp Ins/Del (genotypic, p=0.04) and ii) rs1989787 and rs1611115 (combined genotypic, p=0.004) on Abnormal Involuntary Movement Scale total score. Association of rs1611115 with positive and negative syndrome scale (PANSS) total score (p=0.05) and allelic/genotypic association with lower positive (p=0.03/0.04), general psychopathology (p=0.01/0.01) PANSS scales in tardive dyskinesia-positive; and allelic/genotypic (p=0.02/0.05) with higher score of depressive factors in tardive dyskinesia-negative subgroups were observed. Analysis of covariance with continuous variable of cognition showed interaction of health status with: i) rs1989787 on accuracy and efficiency (p=0.03) of abstraction and mental ?exibility; ii) rs1611115 on accuracy of working memory and emotion (p=0.05); iii) 19bp Ins/Del on processing speed of emotion (p=0.03). Allelic/genotypic association of rs1989787 with spatial ability (p=0.02-0.05) among healthy controls; association of rs1611115 with Global Assessment Scale scores in the past month (p=0.05) among schizophrenia subjects of cognition cohort was also observed.ConclusionsWith modest genotype-phenotype correlations available for DBH variants, personalized treatment regimens based on DBH activity for ameliorating tardive dyskinesia and cognitive symptoms may be plausible.

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

Association between the IL10 rs1800896 Polymorphism and Tardive Dyskinesia in Schizophrenia.

Publications

Association between the IL10 rs1800896 Polymorphism and Tardive Dyskinesia in Schizophrenia.

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