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DRD2/DRD4 heteromerization may influence genetic susceptibility to alcohol dependence

Molecular Psychiatry volume 18, pages 401–402 (2013)Cite this article

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A major limitation of candidate gene studies in psychiatric genetics is the lack of evidence-based hypotheses for the study of gene–gene interactions. An emerging field that may provide such evidence is the analyses of oligomerization of G-protein-coupled receptors such as dopamine receptors (DRs). It has recently been shown that DRD4 and DRD2 are able to form heteromers and that specific variants in both genes may interfere in this process.1, 2 We wondered if this heteromerization process might help to elucidate the controversial but repeated findings regarding DRD4 and DRD2 genes in some behavioral phenotypes.

DRD4 gene has a well-studied 48-bp variable number tandem repeat (VNTR) polymorphism in exon 3. The most common variants are 2-, 4- and 7-repeats (2R, 4R and 7R, respectively), with the last one being frequently associated with psychiatric disorders. DRD2 is expressed in two distinct isoforms, the short variant named D2S (mainly presynaptic) and the long variant named D2L (mainly postsynaptic). The balanced expression of both isoforms may be disrupted by the DRD2 rs2283265 single-nucleotide polymorphism (SNP), where the minor T allele favors the inclusion of the sixth DRD2 exon, switching D2S/D2L balance toward the long form.3 This allele has been associated with reduced working memory and attention control3 and with cocaine abuse.4

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Acknowledgements

This study was supported by the following Brazilian funding agencies: CNPq, CAPES, FAPERGS and DECIT/SCTIE/MS/PPSUS.

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Authors and Affiliations

  1. Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    N R Mota, D L Rovaris, G P Bertuzzi, V Contini, T Roman, S M Callegari-Jacques, M H Hutz & C H D Bau

  2. Department of Psychiatry, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    E S Vitola & E H Grevet

  3. Department of Statistics, Instituto de Matemática, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    S M Callegari-Jacques

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  1. N R Mota
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  2. D L Rovaris
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  3. G P Bertuzzi
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  5. E S Vitola
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  8. S M Callegari-Jacques
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  9. M H Hutz
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  10. C H D Bau
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Correspondence to C H D Bau.

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Mota, N., Rovaris, D., Bertuzzi, G. et al. DRD2/DRD4 heteromerization may influence genetic susceptibility to alcohol dependence. Mol Psychiatry 18, 401–402 (2013). https://doi.org/10.1038/mp.2012.50

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