Association study of the vesicular monoamine transporter gene SLC18A2 with tardive dyskinesia
ABSTRACT Tardive dyskinesia (TD) is an involuntary movement disorder that can occur in up to 25% of patients receiving long-term first-generation antipsychotic treatment. Its etiology is unclear, but family studies suggest that genetic factors play an important role in contributing to risk for TD. The vesicular monoamine transporter 2 (VMAT2) is an interesting candidate for genetic studies of TD because it regulates the release of neurotransmitters implicated in TD, including dopamine, serotonin, and GABA. VMAT2 is also a target of tetrabenazine, a drug used in the treatment of hyperkinetic movement disorders, including TD. We examined nine single-nucleotide polymorphisms (SNPs) in the SLC18A2 gene that encodes VMAT2 for association with TD in our sample of chronic schizophrenia patients (n = 217). We found a number of SNPs to be nominally associated with TD occurrence and the Abnormal Involuntary Movement Scale (AIMS), including the rs2015586 marker which was previously found associated with TD in the CATIE sample (Tsai et al., 2010), as well as the rs363224 marker, with the low-expression AA genotype appearing to be protective against TD (p = 0.005). We further found the rs363224 marker to interact with the putative functional D2 receptor rs6277 (C957T) polymorphism (p = 0.001), supporting the dopamine hypothesis of TD. Pending further replication, VMAT2 may be considered a therapeutic target for the treatment and/or prevention of TD.
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ABSTRACT: Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research.Pharmacogenomics and Personalized Medicine 01/2014; 7:317-28. DOI:10.2147/PGPM.S52806
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ABSTRACT: This review outlines the positive and negative aspects of DNA testing and provides an account of the issues particularly relevant to schizophrenia. Modern technology has changed the field of medicine so rapidly that patients and their families have become much more independent in their healthcare decisions than in the previous decade. Simply by finding information on the Internet, they gain knowledge about disease diagnosis, treatment options and their side-effects. No medical field likely has been more affected and more controversial than that of genetics. It is now possible to sequence the individual human genome and detect single nucleotide variations, microdeletions and duplications within it. Commercial companies have sprung up in a similar manner to the software or electronic industries and have begun to market direct-to-consumer DNA testing. Much of this may be performed to satisfy curiosity about one's ancestry; but commercially available results that appear incidentally can also be distributed to the consumer. Ethicists, genetics researchers, clinicians and government agencies are currently in discussion about concerns raised about commercially available DNA testing, while at the same time recognizing its value in some instances to be able to predict very serious disabilities.Current opinion in psychiatry 03/2014; DOI:10.1097/YCO.0000000000000060 · 3.55 Impact Factor
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ABSTRACT: The XXI World Congress of Psychiatric Genetics (WCPG), sponsored by the International Society of Psychiatric Genetics (ISPG), took place in Boston, Massachusetts, on 17-21 October 2013. Approximately 900 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by student travel awardees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported.Psychiatric Genetics 06/2014; DOI:10.1097/YPG.0000000000000043 · 2.27 Impact Factor