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Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function


Although there is some evidence from twin studies that individual differences in sexual behavior are heritable, little is known about the specific molecular genetic design of human sexuality. Recently, a specific dopamine D4 receptor (DRD4) agonist was shown in rats to induce penile erection through a central mechanism. These findings prompted us to examine possible association between the well-characterized DRD4 gene and core phenotypes of human sexual behavior that included desire, arousal and function in a group of 148 nonclinical university students. We observed association between the exon 3 repeat region, and the C-521T and C-616G promoter region SNPs, with scores on scales that measure human sexual behavior. The single most common DRD4 5-locus haplotype (19%) was significantly associated with Desire, Function and Arousal scores. The current results are consistent with animal studies that show a role for dopamine and specifically the DRD4 receptor in sexual behavior and suggest that one pathway by which individual variation in human desire, arousal and function are mediated is based on allelic variants coding for differences in DRD4 receptor gene expression and protein concentrations in key brain areas.

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  1. Argiolas A, Melis MR . The neurophysiology of the sexual cycle. J Endocrinol Invest 2003; 26(3 Suppl): 20–22.

    CAS  PubMed  Google Scholar 

  2. Melis MR, Succu S, Mascia MS, Argiolas A . PD-168077, a selective dopamine D4 receptor agonist, induces penile erection when injected into the paraventricular nucleus of male rats. Neurosci Lett 2005; 379(1): 59–62.

    Article  CAS  Google Scholar 

  3. Steen KV, Lange C . PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies. Hum Genom 2005; 2(1): 67–69.

    Article  Google Scholar 

  4. Dudbridge F . Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25(2): 115–121.

    Article  Google Scholar 

  5. Okuyama Y, Ishiguro H, Nankai M, Shibuya H, Watanabe A, Arinami T . Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait. Mol Psychiatry 2000; 5(1): 64–69.

    Article  CAS  Google Scholar 

  6. D'Souza UM, Russ C, Tahir E, Mill J, McGuffin P, Asherson PJ et al. Functional effects of a tandem duplication polymorphism in the 5′flanking region of the DRD4 gene. Biol Psychiatry 2004; 56(9): 691–697.

    Article  CAS  Google Scholar 

  7. Van Craenenbroeck K, Clark SD, Cox MJ, Oak JN, Liu F, Van Tol HH . Folding efficiency is rate-limiting in dopamine D4 receptor biogenesis. J Biol Chem 2005; 280(19): 19350–19357.

    Article  CAS  Google Scholar 

  8. Wang E, Ding YC, Flodman P, Kidd JR, Kidd KK, Grady DL et al. The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus. Am J Hum Genet 2004; 74(5): 931–944.

    Article  CAS  Google Scholar 

  9. Bachner-Melman R, Gritsenko I, Nemanov L, Zohar AH, Dina C, Ebstein RP . Dopaminergic polymorphisms associated with self-report measures of human altruism: a fresh phenotype for the dopamine D4 receptor. Mol Psychiatry 2005; 10(4): 333–335.

    Article  CAS  Google Scholar 

  10. Hoon EF, Joon PW, Wincze JP . An inventory for the measurement of female sexual arousability: the SAI. Arch Sex Behav 1976; 5(4): 269–274.

    Article  CAS  Google Scholar 

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This research was partially supported by the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities (RPE) and the Israel Association of University Women (RBM). We would like to thank all the subjects and their family members who so willingly participated in this research.

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Correspondence to R P Ebstein.

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Ben Zion, I., Tessler, R., Cohen, L. et al. Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function. Mol Psychiatry 11, 782–786 (2006).

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  • sexual behavior
  • dopamine D4 receptor gene
  • DRD4
  • polymorphism
  • haplotype
  • family study

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