Minor genetic variants of the dopamine D4 receptor (DRD4) polymorphism are associated with novelty seeking in healthy Japanese subjects

Although an association between the dopamine receptor D4 (DRD4) gene and personality traits had been previously investigated, results from previous studies were not conclusive. This may be due to the method of grouping used, which categorized the gene population into two groups based on the length of the variable number of tandem repeats (VNTR) in exon 3. In the present study, we categorized 616 healthy Japanese subjects into more than two groups by further subdividing the DRD4 48-bp VNTR polymorphism, and compared Temperament and Character Inventory (TCI) scores among the groups. A significant difference was found between the DRD4 48-bp VNTR polymorphism and novelty seeking (p = 0.016). The novelty-seeking scores in the subjects carrying the 5/5 genotype were significantly higher than in those carrying the 2/2 genotype (p = 0.002) or the 4/4 genotype (p = 0.005). However, when the conventional method of grouping was used (i.e., short alleles vs. long alleles), there were no significant associations between the DRD4 VNTR polymorphism and any TCI scores. Our results suggest that minor 5-repeat allele is associated with high novelty-seeking scores in healthy Japanese subjects.     

No association between the TPH A218C polymorphism and personality traits in Japanese healthy subjects

It has been suggested that the central serotonergic activity is implicated in personality traits. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. In the present study, the association between the TPH A218C polymorphism and personality traits assessed by the Temperament and Character Inventory (TCI) was examined in 345 Japanese healthy subjects. The TPH A218C polymorphism was determined by a PCR-RFLP method. There were no significant differences in the seven dimension scores of TCI among the A/A, A/C, and C/C genotype groups by the one-way ANOVA. There was a significant negative correlation between age and the NS scores. Females showed significantly higher scores of HA, RD, and ST, and significantly lower scores of SD than males. The multiple regression analysis using age, gender, and the TPH genotype as independent variables also showed no significant association between any dimension score and the genotype. The present study thus suggests that the TPH A218C polymorphism does not affect personality traits in Japanese healthy subjects.     

Association study of catechol-O-methyltransferase Val158Met polymorphism with personality traits in Japanese healthy volunteers.

Catechol-O-methyltransferase (COMT) is one of the major enzymes for the degradation of catecholamines. It has been suggested that catecholaminergic neurotransmission is involved in characterization of personality. Previous studies on the association between the COMT Val158Met polymorphism and personality traits in healthy subjects have produced inconsistent results. Therefore, the relationship between this polymorphism and personality was re-examined in 478 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the COMT genotypes were determined by a PCR-RFLP method. In total, there were no significant differences among the Val/Val, Val/Met, and Met/Met genotypes in seven TCI dimension scores. Similarly, no significant relationship was found between the COMT genotypes and the TCI dimensions when males and females were analyzed separately. The present study thus suggests that the COMT Val158Met polymorphism is not associated with personality traits in Japanese healthy subjects.     

Association study of the cytochrome P450 17 gene polymorphism with personality traits in healthy subjects

There have been several studies suggesting that sex hormones are involved in characterization of human mental function and behaviour. Recently, it has been reported that the -34T/C polymorphism of cytochrome P450 17 (CYP17) gene affects sex hormone dispositions. Therefore, it is possible that the CYP17 -34T/C polymorphism affects personality traits. In the present study, the association of this genetic polymorphism with personality traits was examined in 595 healthy Japanese. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the CYP17 -34T/C polymorphism was detected by a PCR-RFLP method. In males, the scores of novelty seeking, cooperativeness, and self-transcendence were higher in the group with the C allele than in that without this allele. In females, none of the seven TCI dimensions was different between the two genotype groups. The present study thus suggests that the -34T/C polymorphism of the CYP17 gene affects personality traits of healthy males, but not females, and this gender-dependent effect may be mediated by the action of sex hormones such as estradiol and testosterone.     

Association between the dopamine D2 receptor (DRD2) polymorphism and the personality traits of healthy Japanese participants

Background

Dopamine neurotransmitter systems have been associated with reward-related and novelty-seeking personality traits. We investigated the possible relationship between the personality traits measured by the Temperament and Character Inventory (TCI) and the TaqI A and − 141C Ins/Del polymorphisms in the dopamine D2 receptor gene (DRD2).

Methods

The sample consisted of 1084 healthy Japanese medical students and medical staff (age = 29.0 ± 9.7 years), each of whom completed the TCI. Their genomic DNA was isolated from whole blood and genotyped using the TaqMan allele-specific assay method. The associations between gene polymorphisms and the scores for TCI were statistically analyzed by one-way analysis of covariance (ANCOVA) adjusting age. Males and females were analyzed separately. Epstatis was assesses using two-way ANCOVA between the DRD2 and ANKK1 genes.

Results

Men with the Ins/Del genotype of the − 141C Ins/Del polymorphism had significantly higher self-directedness scores than those with the Ins/Ins genotype (p = 0.021). None of the TCI scores differed among women with regard to the three genotype groups of the − 141C Ins/Del polymorphism. The DRD2/ANKK1 Taq1 A polymorphism did not affect any TCI factor for either men or women. An epistatic analysis did not reveal main effects of the two genes with regard to TCI scores, but an ANKK1 × DRD2 interaction significantly predicted TCI scores.

Conclusion

These findings suggest the possibility that the − 141C Ins/Del polymorphism and the DRD2/ANKK1 Taq1 A polymorphism are not strongly linked to personality traits directly, but influences them under the interaction between the DRD2 and ANKK1 genes.     

Association between monoamine oxidase A (MAOA) and personality traits in Japanese individuals

It has been reported that personality traits are related to several neurotransmitters. However, the association between personality traits and the central nervous system remains unclear. In the present study, we investigated the relationships between a polymorphism involving a variable number of tandem repeats in the promoter of the monoamine oxidase A (MAOA-VNTR) gene and personality traits, as assessed by the Temperament and Character Inventory (TCI). Promoter VNTRs in the MAOA were genotyped in 558 healthy Japanese individuals. Females homozygous for high-activity allele (4/4) had significantly higher persistence scores than those homozygous for the low-activity allele (3/3) (p=0.012, ANOVA). Meanwhile no difference in persistence was found between 3 and 4 allele in males. There were no differences between other scores of TCI subscales and MAOA-VNTR polymorphism. Our results suggest a gender-specific contribution of MAOA-VNTR polymorphism to persistence scores.     

An interaction between the serotonin transporter promoter region and dopamine transporter polymorphisms contributes to harm avoidance and reward dependence traits in normal healthy subjects

Summary. There is evidence for an association between polymorphisms of serotonin- and dopamine-related genes and temperamental personality traits. Recent findings have shown that interactions between allelic variants of the different genes may contribute to personality traits. We examined the effects of serotonin transporter-linked promoter region (5-HTTLPR) and dopamine transporter (DAT1) gene polymorphisms for associations with the Temperament and Character Inventory (TCI) temperament subscales in 209 Koreans. We found that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI. Neither of these two genes affected any subscales of TCI alone. Controlling for the effects of gender and age, we found significant interactions between 5-HTTLPR and DAT1 genes on Harm Avoidance (HA) and Reward Dependence (RD) as measured by the TCI (Hotelling’s Trace = 3.0, P = 0.02). In the presence of the DAT1 10/10 genotype, subjects of group L of 5-HTTLPR had a significantly higher HA score and significantly lower RD score than those of group S (F = 5.04, df = 1, p = 0.03 and F = 8.35, df = 1, p = 0.004, respectively). These findings suggest that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI.     

Serotonin transporter gene polymorphism and personality traits in a Korean population

Recently, there has been growing enthusiasm for exploring biological approaches to personality, especially in the area of genetic research into the identification of those genes responsible for particular personality traits. The aim of this study was to investigate the association between the serotonin transporter-linked promoter region (5-HTTLPR) polymorphism and personality traits. We recruited 211 unrelated, normal subjects. The Korean version of the Temperament and Character Inventory (TCI) was used to assess certain personality traits. From blood samples taken from the subjects, DNA was isolated using standard techniques and the 5-HTTLPR polymorphism was genotyped by means of polymerase chain reaction and electrophoresis. We classified the subject into the s/s, s/l, and l/l groups according to their genotype. The differences in the temperament factors of the TCI between group S (s/s genotype) and group L (s/l + l/l genotype) were assessed, after the inclusion of gender and age as covariates in the analysis of variance. After controlling for gender and age, there were no associations between the harm avoidance, novelty seeking, and reward dependence scores and the genotypes. However, the persistence score of group S was significantly higher than that of group L. Our results suggest that the 5-HTTLPR polymorphism may be associated with the persistence score of the TCI in a normal Korean population.     

Association between angiotensin I-converting enzyme insertion/deletion gene functional polymorphism and novelty seeking personality in healthy females

A certain type of personality is at risk for developing psychiatric diseases. Several lines of evidence support the interaction between brain angiotensins and central catecholamine systems, and suggest that angiotensin I-converting enzyme (ACE) may be a reasonable candidate gene for psychiatric disorders. The present study examined the possibility that ACE insertion (I)/deletion (D) functional polymorphism might be associated with particular personality traits. Healthy Japanese subjects (N=184) were administered the Temperament and Character Inventory (TCI) and the NEO Personality Inventory Revised version (NEO-PI-R), and their ACE I/D polymorphisms were determined. There was an ethnic difference in the genetic distribution of ACE I/D between Japanese (D=34.5%) and Caucasians (D=55.2%). We found that the scores of novelty seeking (NS) in the Low-ACE group (II genotype) of healthy female subjects were significantly lower than those in the High-ACE group (ID or DD genotype) (p=0.018). Our findings suggested that the ACE I/D polymorphism might be associated with the NS personality trait in females, but not males. Taking into account the effects of multiple comparisons, this result should be interpreted with caution, and needs confirmation in a larger sample.     

Association between plasma brain-derived neurotrophic factor levels and personality traits in healthy Japanese subjects

Although depression has been associated with decreased brain-derived neurotrophic factor (BDNF) levels for specific personality traits, there is a little information regarding the association between peripheral BDNF levels and such traits. The sample consisted of 178 healthy Japanese subjects (age range, 37.4±11.5 years). All subjects filled out the Temperament and Character Inventory (TCI). Plasma BDNF levels were measured using the enzyme-linked immunosorbent assay. A simple regression analysis revealed that plasma BDNF levels were significantly correlated with harm avoidance (r=−0.177, p=0.018) and self-directedness scores (r=0.165, p=0.028). Our findings suggest that plasma BDNF levels are associated with depression-related personality traits.     

Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationship to temperamental dimensions measured by the Temperament and Character Inventory in healthy volunteers

There is evidence for an association between polymorphisms of monoamine transporter genes and temperamental personality traits. Recent findings have shown that interaction of allelic variants of the different genes may contribute to the personality factors. We studied the association between temperamental personality dimensions measured with the Temperament and Character Inventory (TCI) and polymorphisms of the dopamine (DAT), norepinephrine (NET) and serotonin (5-HTT) transporter genes in 127 healthy Polish volunteers. There were no significant differences between means of TCI temperamental dimensions (novelty seeking, reward dependence, persistence and harm avoidance) and the transporter genes compared by ANOVA. There were some significant associations between genotypes and TCI subdimensions. Individuals carrying the A9/A9 DAT genotype have lower RD4 scores (dependence vs. independence) than A10/A10 individuals (3.0 +/- 1.4 vs. 3.5 +/- 1.3); p = 0.01. Examining 5-HTT gene promoter polymorphism, heterozygous individuals (l/s) and individuals with 44-bp deletion (s/s) scored significantly lower in the HA1 subdimension (anticipatory worry and pessimism vs. uninhibited optimism; 4.3 +/- 2.3 vs. 5.5 +/- 2.6) in comparison with individuals without deletion (l/l); p = 0.021. The NET transporter gene polymorphism showed no significant association with any of the temperamental TCI subdimensions.     

BDNF serum levels,but not BDNF Val66Met genotype,are correlated with personality traits in healthy subjects

Consisting evidence in animal models has suggested that alterations in brain-derived neurotrophic factor (BDNF) brain expression and release are involved in the pathogenesis of mental illnesses, such as, mood, anxiety, and eating disorders. This hypothesis is supported by data emerging from biochemical studies on serum BDNF levels and genetic studies on the functional polymorphism Val66Met in the BDNF gene in patients and control subjects. Anxiety-related personality traits are associated with several mental disorders. However, they are also measurable in non-affected subjects and, so, may represent a useful “endophenotype” to study the biological correlation of the vulnerability factors in the general population. In this study, we analyzed putative correlations in subjects unaffected by mental disorders between personality traits, serum BDNF levels (N = 107), and the BDNF Val66Met genotype (N = 217). Furthermore, we tested the possible interactions between these variables. A significant correlation has been observed between high scores of harm avoidance (HA) measured by the temperament and character inventory (TCI), and low BDNF serum concentration (r = −0.253, P = 0.009). In addition, an association has been evidenced between low BDNF levels in serum and the BDNF Val/Val genotype (P = 0.021). By analyzing putative concomitant effects of different variables on HA scores in a regression model, we observed a significant correlation only with BDNF serum concentrations (P = 0.022). The study results suggest that a decrease in serum BDNF concentrations may represent a biochemical marker associated with anxiety personality traits also retrievable in the general population.     

An association of the polymorphic repeat of tetranucleotide (TCAT) in the first intron of the human tyrosine hydroxylase gene with schizophrenia in a Japanese sample

Summary. Tyrosine hydroxylase (TH) is the rate limiting enzyme in the synthesis of dopamine and norepinephrine. A polymorphic repeat of the tetranucleotide (TCAT) in the first intron of the TH gene may behave as a regulatory element for the gene expression. Allelic fragments of the tandem repeat were typed by a PCR-based process with a pair of primers specific for the polymorphic sequence. The association between the polymorphism and schizophrenia was examined in a Japanese sample. There was a statistically significant association between the polymorphism and schizophrenia in females (χ² = 26.018, p = 0.010), but not in males (χ² = 15.995, p = 0.305). The genotype heterozygous for the TH9 and TH6 was significantly decreased in female schizophrenics (χ² = 5.125, p = 0.0236). These results suggest that TH could be considered as a minor gene contributing to the susceptibility of Japanese female schizophrenia. Received July 18, 2000; accepted November 3, 2000     

No association between the Clara cell secretory protein (CC16) gene polymorphism and personality traits

Clara cell secretory protein (CC16) is an anti-inflammatory protein expressed in the respiratory tract. Several studies have suggested the association between CC16 and mental disturbances, such as schizophrenia, depression, and post-traumatic stress disorder. In the present study, we investigated the association between the CC16 gene A38G polymorphism and personality traits in 214 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the genotypes and the scores of the NEO PI-R or the STAI. The present results suggest that CC16 may not have a major role in the development of personality traits.     

No association of DRD2, DRD3, and tyrosine hydroxylase gene polymorphisms with personality traits in the Japanese population

Background  

Dopamine D2 receptor (DRD2) and dopamine D3 receptor (DRD3) genes could be candidates for personality-related genes considering their pharmacological profiles or structures. However, a limited number of studies have investigated the association between these genes and personality traits. In the present study, we investigated the DRD2, DRD3, and tyrosine hydroxylase (TH) genes in relation to personality traits in the Japanese population. Epistasis (gene-gene interaction) among the genes was extensively analyzed, in addition to the analysis based on each gene.     

Interaction between serotonin 5-HT2A receptor gene and dopamine transporter (DAT1) gene polymorphisms influences personality trait of persistence in Austrian Caucasians

We examined 89 normal volunteers using Cloninger's Temperament and Character Inventory (TCI). Genotyping the 102T/C polymorphism of the serotonin 5HT2A receptor gene and the ser9gly polymorphism in exon 1 of the dopamine D3 receptor (DRD3) gene was performed using PCR-RFLP, whereas the dopamine transporter (DAT1) gene variable number of tandem repeats (VNTR) polymorphism was investigated using PCR amplification followed by electrophoresis in an 8% acrylamide gel with a set of size markers. We found a nominally significant association between gender and harm avoidance (P=0.017; women showing higher scores). There was no association of either DAT1, DRD3 or 5HT2A alleles or genotypes with any dimension of the TCI applying Kruskal–Wallis rank-sum tests. Comparing homozygote and heterozygote DAT1 genotypes, we found higher novelty seeking scores in homozygotes (P=0.054). We further found a nominally significant interaction between DAT1 and 5HT2A homo-/heterozygous gene variants (P=0.0071; DAT1 and 5HT2A genotypes P value of 0.05), performing multivariate analysis of variance (MANOVA). Examining the temperamental TCI subscales, this interaction was associated with persistence (genotypes: P=0.004; homo-/heterozygous gene variants: P=0.0004). We conclude that an interaction between DAT1 and 5HT2A genes might influence the temperamental personality trait persistence.     

Serotonin Transporter Gene Polymorphism and Schizoid Personality Traits in Patients with Psychosis and Psychiatrically Well Subjects

Background and Objectives: Serotonin transporter (5-HTT) gene allelic variants were shown to be associated with Neuroticism and Harm Avoidance but the results were not replicated in other studies. The current investigation was undertaken in a further attempt to study the relationship between 5-HTT polymorphism and personality traits.

Subjects and Methods: To evaluate a spectrum of personality traits, MMPI was administered to a sample including patients with affective disorders (n=114), patients with schizophrenia spectrum illnesses (n=110) and psychiatrically well controls (n=124). All groups were genotyped for VNTR-17 and functional insertion-deletion (5-HTTLPR) polymorphisms.

Results: An association was found between 5-HTTLPR polymorphism and scores on three MMPI scales: Psychopathic deviance, Paranoia and Schizophrenia in patients with affective disorders and Schizophrenia in normal subjects. Both affected and control individuals with ‘ss’ genotype exhibited lower scores on these scales.

Conclusion: We demonstrated that functional deletion/insertion allelic variation associated with decreased expression of serotonin transporter (‘s’ allele or ‘ss’ genotype) may restrict expression of schizoid traits in normal subjects and patients with affective disorders.     

Functional polymorphism of the glutathione peroxidase 1 gene is associated with personality traits in healthy subjects

BACKGROUND: Several lines of evidence suggest that a certain type of personality or temperament as well as oxidative stress may be implicated in the pathophysiology of neuropsychiatric diseases. Glutathione peroxidase 1 (GPX1) plays a role in the antioxidant defense system. OBJECTIVES: The authors studied the association between the GPX1 gene polymorphism and personality traits in healthy subjects. METHODS: One hundred forty-nine healthy subjects were enrolled. Analysis of the functional polymorphism (Pro198Leu) in the human GPX1 gene was performed. RESULTS: Subjects with Pro198Pro have significantly higher scores in openness to experience on the Revised NEO Personality Inventory (NEO-PI-R) as compared with subjects with other genotypes (Pro198Leu or Leu198Leu). In contrast, we detected no association between other personality dimensions on the NEO-PI-R and scores on the Temperament and Character Inventory. CONCLUSION: This study reports that the functional polymorphism (Pro198Leu) in the GPX1 gene might be associated with openness to experience among the personality traits.     

Association between serotonin transporter gene polymorphism and anxiety-related traits.

BACKGROUND: Polymorphism in the serotonin transporter promoter gene has been recently reported to be associated with the personality trait known as anxiety-related traits. We have attempted to replicate these findings in 101 healthy Japanese subjects. METHODS: The personality traits of the subjects were assessed with the tridimensional personality questionnaire. RESULTS: An association was observed in the present study between individuals grouped according to the transporter gene and harm avoidance scores. CONCLUSIONS: These data supported that there was an association between the serotonin transporter gene and anxiety.