Global variation of a 40-bp VNTR in the 3′-untranslated region of the dopamine transporter gene (SLC6A3)

Background: The dopamine transporter (DAT) is the primary mechanism for dopamine clearance from the synapse in midbrain dopaminergic neurons, and the target of psychostimulant and neurotoxic drugs such as cocaine, amphetamine, and MPTP. Consequently, the gene for DAT (SLC6A3) has been the focus of many population-based case-control association studies using a 40-bp VNTR in the 3'-untranslated region. Results have differed depending on the population studied, suggesting allele frequency effects are involved. For this reason, a global survey of allele frequencies for this VNTR polymorphism was performed. Methods: Individuals (n = 1528) from 30 populations around the world were typed for this VNTR using PCR and agarose gel electrophoresis. Results: As with previous studies, the ten-repeat allele is most common, except for a Middle Eastern population in which the nine-repeat allele is most frequent. Frequencies of the nine- and ten-repeat alleles vary widely even among European populations. Conclusions: Many previous association studies have used "white" or "black" U.S. populations. However, many different ethnic groups have contributed to these populations. The large variation in allele frequencies observed in this study emphasizes the inadequacy of most past studies using the case-control design and the importance of matching patient and control populations in future association studies. (C) 1999 Society of Biological Psychiatry.