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No association of the −521 C/T polymorphism in the promoter of DRD4 with novelty seeking

Molecular Psychiatry volume 6, pages 618–619 (2001)Cite this article

SIR – Since the original reports of an association between Novelty Seeking (NS) and a 48-basepair repeat polymorphism in the DRD4 gene,1,2 several groups have published both positive and negative replication studies.3,4,5,6,7,8,9,10,11 These somewhat contradictory results suggest the possibility that the 48-bp repeat polymorphism is merely in linkage disequilibrium with another polymorphism actually influencing NS. It was therefore of interest when Okuyama et al12 reported a statistically significant association (P = 0.0001) between the C allele of a −521C/T polymorphism of the DRD4 promoter and high NS scores. These authors also found that the T-variant of the polymorphism reduces transcriptional efficiency in vitro and thus, this polymorphism might be functional in vivo. Recently, Ronai et al13 confirmed association with the promoter polymorphism and NS (P < 0.01) in 109 healthy university and high school students. Here we attempt to replicate this finding in a sample consisting of extreme NS scorers from a population-wide birth cohort in northern Finland. The study sample has been described previously4 and consists of 50 females and 50 males with either extremely high or extremely low scores on NS (n = 200). We found no association between NS and the −521C/T polymorphism of the DRD4 promoter region (P = 0.91). This polymorphism can not have an important role in regulating NS scores, at least in the Finnish population.

Several studies have reported an association between the human personality trait of Novelty Seeking14 and a 48-bp repeat in the dopamine receptor 4 gene (DRD4).1,2,3,8,9 This polymorphism is thought to be functional, affecting clozapine and spiperone binding.15 Several studies have also been published in which the association either has not been replicated or has been in the opposite direction.4,5,6,7,10,11 It is therefore possible that this polymorphism in itself does not influence NS scores, but that it is merely in linkage disequilibrium with the variant that actually affects NS. Any polymorphism within the DRD4 gene, its promoter or within any gene in the close vicinity of DRD4 is therefore a putative candidate for a functional variant affecting NS scores.

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Authors and Affiliations

  1. Department of Mlecular Medicine, National Public Health Institute, Helsinki, Finland

    J Ekelund, J Suhonen, L Peltonen & D Lichtermann

  2. Departments of Public Health and General Medicine, University of Oulu, Oulu, Finland

    M-R Järvelin

  3. Department of Human Genetics, UCLA School of Medicine, CA, USA

    L Peltonen

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  1. J Ekelund
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  2. J Suhonen
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  3. M-R Järvelin
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  4. L Peltonen
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  5. D Lichtermann
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Correspondence to J Ekelund.

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Ekelund, J., Suhonen, J., Järvelin, MR. et al. No association of the −521 C/T polymorphism in the promoter of DRD4 with novelty seeking. Mol Psychiatry 6, 618–619 (2001). https://doi.org/10.1038/sj.mp.4000943

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