In the present study, we investigated the association of polymorphisms in the three dopamine-related genes, DRD2, DRD3, and TH, with personality traits. Epistasis among the genes was extensively analyzed, in addition to the analysis based on each gene. As a result, in the analysis based on each gene, trends for association were observed between State Anxiety and the DRD2 -141C Ins/Del polymorphism (p = 0.031, uncorrected), and between Trait Anxiety and the DRD2 Ser311Cys or TH PstI site polymorphism (p = 0.048 and 0.041, respectively, uncorrected). In epistatic analysis, a trend for interaction was observed on the scores for Neuroticism and Trait Anxiety between the DRD2 -141C Ins/Del and TH Val81Met polymorphisms (p = 0.015 and 0.010, respectively, uncorrected). However, these differences were insignificant after Bonferroni correction. Thus, the present study did not provide evidence for the association between these dopamine-related genes, DRD2, DRD3, and TH, and personality traits in Japanese subjects.
No association between the Ser311Cys polymorphisms in the DRD2 gene and personality traits in the present result was consistent with the previous study [10]. With respect to the DRD2 -141C Ins/Del polymorphism, the result was consistent with the previous Japanese study [14], indicating no significant association between the polymorphism and personality traits. Jonsson et al. [13] also observed no association between the polymorphism and the score for the Temperament and Character Inventory (TCI) [29] in Caucasian, although the association with detached personality was observed. The role of DRD2 in personality traits may be relatively small considering no association of two major functional polymorphisms. However, in the present result, the score for State or Trait Anxiety increased consecutively according to the amount of -141C Ins or 311 Ser variant, respectively. It may be worth investigating further in a larger sample, because low frequency of the -141C Del or 311 Cys variant might cause insufficient statistical power.
No significant association was observed between personality traits and DRD3 or TH polymorphisms in the present study. To our knowledge, this is the first to investigate the relation between the TH Val81Met or PstI site polymorphism and personality traits. With respect to the DRD3 Ser9Gly polymorphism, the result was consistent with the previous studies [19,20]. Ebstein et al. [18] observed a significant interaction among three gene polymorphisms, the DRD3, DRD4, and 5-HT2C, on personality trait of reward dependence. In epistatic analysis of the present study, no significant interaction was observed among the genes analyzed after Bonferroni correction.
Several limitations might be considered for the present study. First is the sex unbalancing in the subjects, although sex was included as a covariate in the analyses. Second, the subjects were recruited from the hospital staff, which may not represent the general population sufficiently. Uncontrolled socio-demographic factors might affect the result. Lastly, mood fluctuation of the subjects might affect the measurement of personality traits to some extent.
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