No Association between Dopamine D4 Receptor Gene –521 C/T Polymorphism and Tardive Dyskinesia in Schizophrenia

Na, Kyoung-Sae; Choi, Jung Eun; Paik, Jong Woo; Kim, Yong Ku; Kim, Seung Hyun; Lee, Min Soo; Joe, Sook Haeng; Jung, In Kwa; Lee, Heon Jeong

doi:10.1159/000103576

Cited by 27 publications

(18 citation statements)

References 55 publications

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“…All subjects had been maintained on stable dosages of antipsychotics for at least 3 months prior to the assessment of TD. Other findings from these subjects have been reported previously [17][18][19] . We rated the first 7 items of the AIMS to determine the total AIMS score for abnormal movements.…”

Section: Methodssupporting

confidence: 83%

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Val158Met Polymorphism in the Catechol-O-Methyltransferase (COMT) Gene Is Not Associated with Tardive Dyskinesia in Schizophrenia

Na¹,

Choi²,

Park

et al. 2008

Neuropsychobiology

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Objective: This study investigated whether the catechol-O-methyltransferase (COMT) gene V158M single-nucleotide polymorphism (SNP) influences susceptibility to tardive dyskinesia (TD). Methods: We examined 209 Korean schizophrenic patients using the Abnormal Involuntary Movement Scale (AIMS), with genotyping performed for the COMT gene V158M SNP. Results: The logistic regression analysis showed that old age [p = 0.032, OR = 1.40 (OR corresponds to 10-year), 95% CI = 1.03–1.90] was a risk factor for TD, but there was no significant association between the COMT genotype and TD. The heterozygotes (MV genotype) of the COMT gene polymorphism tended to develop TD less than homozygotes (MM and VV); however, the risk did not reach statistical significance (p = 0.050, OR = 1.81, 95% CI = 1.00–3.29). Conclusions: These results suggest that the V158M SNP of the COMT gene is not associated with TD in schizophrenia. However, there is a tendency that the heterozygous genotype of the COMT gene polymorphism has a protective effect against TD. Further investigations are warranted to evaluate a molecular heterosis of this polymorphism in development of TD in a large sample of subjects.

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Section: Methodssupporting

confidence: 83%

“…The overall genotype distribution of the COMT gene V158M SNP was within the Hardy-Weinberg equilibrium ( 2 = 0.04, p = 0.851). We have previously described the sociodemographic and clinical variables of the patients included in the present study [17] .…”

Section: Resultsmentioning

confidence: 99%

Val158Met Polymorphism in the Catechol-O-Methyltransferase (COMT) Gene Is Not Associated with Tardive Dyskinesia in Schizophrenia

Na¹,

Choi²,

Park

et al. 2008

Neuropsychobiology

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“…None of the patients had a significant comorbid neurological illness, mental retardation, or substance abuse, and all of them were inpatients at the three collaborating hospitals of Korea University hospital. Some findings from these subjects have been reported previously (Lee et al, 2007). Assessment with Abnormal Involuntary Movement Scale (AIMS) was used to recruit 83 schizophrenic patients with TD.…”

Section: Methodsmentioning

confidence: 98%

No evidence for an association between G protein β3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia

Paik

Lee

et al. 2007

Human Psychopharmacology

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“…Candidate gene studies (Kaiser et al 2002; Herken et al 2003; Matsumoto et al 2004; Lai et al 2005; Lerer et al 2005; Patsopoulos et al 2005; Reynolds et al 2005; Bakker et al 2006; Lee et al 2007) and GWAS (Thelma et al 2008 and references therein; Åberg et al 2010; Müller et al 2013 and references therein) have produced results that are largely inconsistent or that fail to reach high statistical significance, mostly owing to low power resulting from small sample size. Armed with so little information about intrinsic vulnerability, the physician not only is unable to predict whether a patient will develop TD but, in the absence of efficacious treatments, also can expect that many of those for whom haloperidol is prescribed will be left with a permanently disfiguring condition.…”

mentioning

confidence: 99%

Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis

et al. 2014

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Haloperidol is an efficacious antipsychotic drug that has serious, unpredictable motor side effects that limit its utility and cause noncompliance in many patients. Using a drug–placebo diallel of the eight founder strains of the Collaborative Cross and their F1 hybrids, we characterized aggregate effects of genetics, sex, parent of origin, and their combinations on haloperidol response. Treating matched pairs of both sexes with drug or placebo, we measured changes in the following: open field activity, inclined screen rigidity, orofacial movements, prepulse inhibition of the acoustic startle response, plasma and brain drug level measurements, and body weight. To understand the genetic architecture of haloperidol response we introduce new statistical methodology linking heritable variation with causal effect of drug treatment. Our new estimators, “difference of models” and “multiple-impute matched pairs”, are motivated by the Neyman–Rubin potential outcomes framework and extend our existing Bayesian hierarchical model for the diallel (Lenarcic et al. 2012). Drug-induced rigidity after chronic treatment was affected by mainly additive genetics and parent-of-origin effects (accounting for 28% and 14.8% of the variance), with NZO/HILtJ and 129S1/SvlmJ contributions tending to increase this side effect. Locomotor activity after acute treatment, by contrast, was more affected by strain-specific inbreeding (12.8%). In addition to drug response phenotypes, we examined diallel effects on behavior before treatment and found not only effects of additive genetics (10.2–53.2%) but also strong effects of epistasis (10.64–25.2%). In particular: prepulse inhibition showed additivity and epistasis in about equal proportions (26.1% and 23.7%); there was evidence of nonreciprocal epistasis in pretreatment activity and rigidity; and we estimated a range of effects on body weight that replicate those found in our previous work. Our results provide the first quantitative description of the genetic architecture of haloperidol response in mice and indicate that additive, dominance-like inbreeding and parent-of-origin effects contribute strongly to treatment effect heterogeneity for this drug.

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No Association between Dopamine D4 Receptor Gene –521 C/T Polymorphism and Tardive Dyskinesia in Schizophrenia

Cited by 27 publications

References 55 publications

Val158Met Polymorphism in the Catechol-<i>O</i>-Methyltransferase (<i>COMT)</i> Gene Is Not Associated with Tardive Dyskinesia in Schizophrenia

Val158Met Polymorphism in the Catechol-<i>O</i>-Methyltransferase (<i>COMT)</i> Gene Is Not Associated with Tardive Dyskinesia in Schizophrenia

No evidence for an association between G protein β3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia

Genetics of Adverse Reactions to Haloperidol in a Mouse Diallel: A Drug–Placebo Experiment and Bayesian Causal Analysis

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