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The DRD3 rs6280 polymorphism and prevalence of tardive dyskinesia: a meta-analysis

Huei-Ting Tsai1, Kari E North, Suzanne L West

  • 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. tsaih2@mail.nih.gov

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
|April 10, 2009
PubMed

Insights

This meta-analysis found no significant association between DRD3 rs6280 gene polymorphisms and the prevalence of tardive dyskinesia (TD). The study suggests that genetic variations in DRD3 may not be a major factor in TD development.

Area of Science:

  • Genetics
  • Neuroscience
  • Pharmacogenomics

Background:

  • Tardive dyskinesia (TD) is a potentially irreversible neurological disorder associated with long-term use of dopamine receptor blocking agents.
  • A specific polymorphism, rs6280, in the dopamine receptor D3 gene (DRD3) has been investigated for its potential association with TD, but findings remain inconclusive.

Purpose of the Study:

  • To systematically evaluate the association between the DRD3 rs6280 polymorphism and the prevalence of tardive dyskinesia (TD) through a comprehensive meta-analysis.
  • To investigate potential sources of heterogeneity in previous studies examining this association.

Main Methods:

  • A systematic literature search was conducted across multiple bibliographic databases to identify relevant studies published between 1997 and 2008.
  • Meta-analysis was performed using prevalence odds ratios (POR) under general, dominant, and recessive inheritance models, with assessments for funnel plot asymmetry and heterogeneity.
  • Stratified analyses were conducted based on study characteristics such as publication year, TD assessment method, TD assessment frequency, patient age, sex, and ancestry.

Main Results:

  • Thirteen eligible studies were included in the meta-analysis.
  • Evidence of funnel plot asymmetry was observed in the general and dominant models, indicating potential publication bias or other systematic differences.
  • Stratified analyses revealed that publication year, TD assessment method/frequency, patient age, sex, and ancestry influenced the observed PORs.
  • Under the recessive inheritance model, the summary estimate was POR = 0.93 (95% CI: 0.70-1.23), suggesting no significant association.

Conclusions:

  • The meta-analysis concludes that there is no or minimal association between the DRD3 rs6280 polymorphism and the prevalence of tardive dyskinesia.
  • Heterogeneity and funnel plot asymmetry in dominant and general models precluded robust summary estimates for these inheritance patterns.
  • The findings suggest that DRD3 rs6280 genotype is unlikely to be a significant risk factor for TD prevalence across diverse populations.

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