Relationship between SLC6A3 genotype and striatal dopamine transporter availability: a meta-analysis of human single photon emission computed tomography studies

The human dopamine transporter (DAT) gene (SLC6A3) contains a 40-bp variable number of tandem repeats (VNTR) polymorphism. A number of studies have investigated the association of this VNTR with striatal DAT availability in humans using single photon emission computed tomography (SPECT). However, the results are not consistent. Therefore, we carried out a meta-analysis of the association between the SLC6A3 VNTR and striatal DAT binding measured in human SPECT studies. The meta-analysis of five samples of healthy individuals failed to find a significant difference in DAT availability between SLC6A3 9-repeat carriers and 10-repeat homozygotes (P = 0.22) although the 9R carriers had nominally higher striatal DAT levels (g = 0.66). The results remained nonsignificant after the inclusion of patient samples, namely schizophrenia, attention deficit hyperactivity disorder, and Parkinson's disease (four samples; all P > 0.18). To conclude, this meta-analysis provides no evidence to support the hypothesis that the SLC6A3 VNTR is significantly associated with interindividual differences in DAT availability in the human striatum. Further work is needed to clarify the molecular mechanisms by which this polymorphism may affect cognition and psychiatric disorders, if not through altered expression as measured by molecular imaging.