Meta-analysis shows schizophrenia is not associated with the 40-base-pair repeat polymorphism of the dopamine transporter gene.
OBJECTIVE
Several case-control studies examined an association between schizophrenia and the 40-bp variable number tandem repeat (VTNR) polymorphism in the 3'-UTR of the dopamine transporter gene (SLC6A3). The results of these studies have been equivocal due to small sample size and low power. This meta-analysis has the aim to evaluate the collective evidence for an association between the VTNR polymorphism and schizophrenia.


METHODS
Different meta-analyses were performed, sequentially considering the 9- and 10-repeat alleles and different genotypes (genotypes 9/9, 9/10, 10/10) as risk factors for schizophrenia. Analyses of the alleles included 659 cases and 563 controls from six case-control studies.


RESULTS
The pooled OR from each analysis approximated 1.0, and none were significant. Lack of significance attributable to the negative effects of single large studies or to heterogeneity between the studies was excluded.


CONCLUSIONS
Despite over 90% power to detect a significant odds ratio as small as 1.3, no association was observed. Considering the cumulative evidence from six case-control studies and results from additional family-based studies, it seems unlikely that the 40-base-pair VTNR polymorphism of the SLC6A3 gene influences risk for schizophrenia.
Gamma
F
F
Department of Psychiatry, Harvard Medical School at the Massachusetts Mental Health Center, Boston, MA, USA. franziska.gamma@verizon.net
Faraone
Stephen V
SV
Glatt
Stephen J
SJ
Yeh
Yu-Chi
YC
Tsuang
Ming T
MT
D000483:Alleles; D050483:Dopamine Plasma Membrane Transport Proteins; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human