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 of VNTR polymorphisms in the MAOA promoter and DRD4 exon 3 with heroin dependence in male Chinese addicts

Objective. To explore the involvement of variable number tandem repeat (VNTR) polymorphisms in the monoamine oxidase A (MAOA) promoter and exon 3 of the dopamine D4 receptor (DRD4) gene in heroin addiction modulate the vulnerability of individuals to heroin addiction. Methods. Eight hundred and ninety-four male heroin addicts without other psychiatric disorders, were recruited as subjects. Another community 180 males were selected randomly as controls. Results. The geno-distribution of the DRD4 exon 3 VNTR polymorphism in controls was in Hardy–Weinberg equilibrium (HWEχ²=0.925), but the distribution in heroin addicts was not (HWEχ²=28.35). The long-repeat alleles of the DRD4 exon 3 VNTR polymorphism were found more frequently in the heroin addicts (P=0.019). However, the long-repeat alleles of the MAOA promoter VNTR polymorphism were not (P=0.828). No interaction between these two VNTR polymorphisms was found by using multiple logistic regression analysis (P=0.261). Conclusion. The long-repeat allelic variants (>4-repeats) and 2-repeat allele of the DRD4 exon 3 VNTR polymorphism might be risk alleles for individual vulnerability to heroin addiction in Chinese men, but the MAOA promoter VNTR polymorphism does not mean that the partial dominant inherited mode might involved in the genetics of heroin dependence.     

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.     

Dopamine D4 receptor 48-bp repeat polymorphism: no association with response to antipsychotic treatment, but association with catatonic schizophrenia

The dopamine D4 receptor (DRD4) may play a role in the pathogenesis of neuropsychiatric disease and in the action of dopaminergic drugs. The 48-bp repeat polymorphism (48-bp VNTR) coding for a 16-amino acid segment in the third cytoplasmatic loop of the DRD4 was studied as a predictor of the therapeutic response to antipsychotics and as susceptibility factor for schizophrenia. We included 638 in-patients with acute schizophrenic, schizoaffective (mainly schizophrenic), and other nonaffective psychoses, as well as two reference groups: one with 278 in-patients with non-psychiatric diseases, and one with 474 healthy volunteers. Catatonic patients (DSM-IV 295.2) more frequently carried the DRD4 D4.2 and D4.3 allele than did all other schizophrenic cases (P < 0.001; OR: 2.7; CI: 1.5-4.9) and controls (P < 0.004; OR: 2.3; CI: 1.3-4.2). We found no significant difference in the DRD4 allele or in genotype frequencies in our comparison of all schizophrenic patients and controls. The subgroups with affected family members, and the subgroups with early or late onset of disease, also did not differ from the controls in DRD4 allele frequencies. The 48-bp VNTR was not a predictor for therapeutic outcome measured by the positive and negative symptoms scale. A total of 1390 subjects showed between 1 and 10 repeats (D4. 1 and D4.10), with 25 different genotypes. These data exclude a major role of DRD4 48-bp VNTR in response to antipsychotic therapy and as susceptibility factor for schizophrenia, but catatonic schizophrenia may be associated with the D4.2 and D4.3 alleles.     

No association between polymorphism in tyrosine hydroxylase and personality traits in healthy Japanese subjects

The aim of the present study was to investigate whether there is an association between the (TCAT)_n repeat polymorphism in the tyrosine hydroxylase (TH) gene and personality. The (TCAT)_n repeat polymorphism in the TH gene was genotyped in 898 healthy Japanese subjects. Personality traits were evaluated using the Temperament and Character Inventory (TCI). There was no significant difference in the TCI scores of subjects with and without the T9 allele. Furthermore, no significant association was found between each genotype and the TCI scores, even when the TCI scores were compared with the homozygous genotype. These findings suggest that the (TCAT)_n repeat polymorphism in the TH gene does not contribute to the personality traits evaluated on the TCI in healthy Japanese subjects.     

<Emphasis Type="Italic">DAT1</Emphasis> and <Emphasis Type="Italic">DRD4</Emphasis> genes involved in key dimensions of adult ADHD

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder often persisting in adulthood. Genetic studies of ADHD mainly focused on the Dopamine Transporter (DAT1) and the Dopamine Receptor 4 (DRD4) genes. Nevertheless, polymorphisms of these genes explain only a small fraction of the assigned risk, suggesting that intermediate dimensions and environmental factors should also be considered. We investigated in 77 adult ADHD subjects compared to 474 controls, how polymorphisms within the genes coding for DAT1 (40-bp VNTR in 3′UTR), the Dopamine Receptor 2 (DRD2) (rs1799732) and DRD4 (48-bp VNTR in exon 3), may modulate the expression of the disorder. By genotyping DAT1, we detected a new 9.5R allele showing a deletion of 40 bp and also an insertion of 19 bp compared to the 10R allele. This novel allele was found to be significantly protective for ADHD (p < 0.0001). Another significant difference was found in the distribution of DRD4 48-bp VNTR 6R allele when comparing patients and controls (p = 0.0007). In addition significant results were also found for DAT1 9.5R allele, which was associated with impulsiveness (p = 1.98 × 10^?4) and trait anger scores (p = 7.66 × 10^?4). Moreover, impulsiveness scores were partly modulated by an interaction between the DRD4 48-bp VNTR 6R allele and childhood maltreatment (p = 0.01), however, this result did not resist correction for multiple comparisons. Altogether, our results show the putative involvement of DAT1 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder.     

Dopamine D4 receptor (DRD4) polymorphism and adaptability trait during infancy: a longitudinal study in 1- to 5-month-old neonates

We have examined the relationship between the common dopamine D4 receptor (DRD4) exon III repeat polymorphism and infants' behavior measured with the Italian version of the Early and Revised Infancy Temperament Questionnaires (EITQ/RITQ) in 122 Italian neonates at 1 and 5 months of life, when the genetic contribution to the behavior can be more clearly assessed. Two-way (genotype × age) analysis of variance revealed a significant correlation with the temperamental subscale of adaptability [F(1, 120)=5.26, P<0.02]. At 1 month of life (early assessment), infants with long (L) DRD4 alleles presented significantly low scores (L 2.61±0.073; S 2.84+0.79; Newman-Keuls P=0.03) in comparison with the high scores of infants with short (S) alleles (L 2.4±0.059; S 2.25±0.57). These differences were not detected at 5 months of life (late assessment), denoting a strong environmental effect at this age on the genetic background. These results confirm and extend the genetic influence of the DRD4 gene in human temperament at birth. Electronic Publication     

Polymorphic variation in the dopamine D4 receptor predicts delay discounting as a function of childhood socioeconomic status: evidence for differential susceptibility

Inconsistent or null findings among studies associating behaviors on the externalizing spectrum—addictions, impulsivity, risk-taking, novelty-seeking traits—with presence of the 7-repeat allele of a common length polymorphism in the gene encoding the dopamine D4 receptor (DRD4) may stem from individuals’ variable exposures to prominent environmental moderators (gene × environment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-repeat allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-repeat allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participants’ early life circumstances, accords with a recently proposed developmental model of gene × environment interaction (‘differential susceptibility’) that posits genetically modulated sensitivity to both adverse and salubrious environmental influences.     

Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis

D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, −141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and −521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p = 0.04, odds ratio (OR) = 0.42, 95% CI; 0.27–0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p = 0.014, OR = 0.34, 95% CI; 0.22–0.54). The genotype of −141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p = 0.00037, OR = 3.62, 95% CI 2.48–5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.     

Association of DRD4 exon III polymorphism with auditory P300 amplitude in 8-year-old children

Summary. Objectives: The present study was designed to investigate the association between the DRD4 genotype and auditory P300 amplitudes in a high-risk community sample. Methods: ERPs were elicited in 197 eight-year-olds (98 boys, 99 girls) using a passive and an active oddball task. Auditory stimuli of 60 dB HL were presented binaurally at 1000 (standard stimulus) and 2000 Hz (target stimulus), at a relative frequency ratio of 80:20. Two trial blocks of 250 stimuli each were collected. P300 amplitudes were analyzed from Fz, Cz and Pz. DNA was genotyped for the DRD4 exon III polymorphism. Results: A pattern of significant interactions of the DRD4 genotype with gender and experimental conditions was obtained. In both the active and the passive task, boys with at least one copy of the DRD4 7-repeat allele displayed significantly lower P300 amplitudes during the second trial block than boys carrying other alleles. Conclusions: This finding provides further evidence supporting a role of P300 amplitude reduction as an endophenotype for disinhibited psychopathology.     

Molecular genetic contribution to the developmental course of attention-deficit hyperactivity disorder

Objective  The developmental trajectory of attention-deficit hyperactivity disorder (ADHD) is variable. Utilizing a longitudinally assessed sample, we investigated the contribution of susceptibility gene variants, previously implicated through pooled or meta-analyses, to the developmental course of Attention-Deficit Hyperactivity Disorder over time. Methods  151 children (aged 6–12) who met diagnostic criteria for ADHD were assessed using research diagnostic interviews during childhood and 5 years later in adolescence. Severity was defined as total number of ADHD symptoms at baseline and reassessment. Association with variants at DRD4, DRD5, and the dopamine transporter gene, DAT was analyzed using linear regression. Results  As expected, affected individuals showed a decline in ADHD severity over time. The DRD4 48 bp VNTR 7-repeat and DRD5 CA(n) microsatellite marker 148 bp risk alleles were associated with persistent ADHD. Those possessing the DRD4 7 repeat risk allele showed less of a decline in severity at reassessment than those without the risk allele. Conclusions  Those carrying the DRD4 7 risk allele showed greater symptom severity at follow-up and less ADHD reduction over time. These findings support the hypothesis that some susceptibility genes for ADHD also influence its developmental course.     

Transmission disequilibrium studies in early onset of obsessive–compulsive disorder for polymorphisms in genes of the dopaminergic system

The dopaminergic system has been shown to be involved in the aetiology of obsessive–compulsive disorder (OCD). Family studies suggest a higher genetic loading in patients with early onset OCD. Our investigation is the first family-based association study concerning polymorphisms in genes of the dopaminergic system in early onset OCD. We studied polymorphisms within the dopamine-4 receptor gene (DRD4), the dopamine transporter gene (DAT1) and the catecholamine-O-methyltransferase gene (COMT). Associations of alleles of DRD4 and COMT with OCD have previously been reported in adults, while a trend towards an association was found for DAT1 alleles. In our study we observed transmission disequilibrium for the 48-bp repeat polymorphism of the DRD4 gene using the ETDT (P = 0.047) in 69 trios comprising patients with early onset OCD and both of their parents. Post hoc TDT analysis of the DRD4 showed reduced transmission of the 4-repeat allele and a slightly increased transmission rate for the 7- and the 2-repeat allele. No evidence of transmission disequilibrium was detected for alleles of the DAT1 and COMT polymorphisms. These polymorphisms do not appear to play a major role in the genetic predisposition to early onset OCD in our study group.     

Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an association study

Objective

To investigate the association between dopaminergic polymorphisms [DRD2 −141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia.

Methods

Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria) [mean age (SD) = 36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean age (SD) = 40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There was a significant difference in genotype distribution for the DRD2 −141C Ins/Del polymorphism [(χ² (2) = 12.35, corrected p = 0.012]. The − 141C Del allele was more common in patients than in controls [0.19 vs. 0.13; χ² (1) = 9.14, corrected p = 0.018, OR (95% CI) = 1.57 (1.17–2.10)]. Genotype and allele distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both groups. However, there was tentative evidence of an interaction effect between DRD3 Ser9Gly and SLC6A3 VNTR [Wald = 9.56 (4), p = 0.049]. Compared to the SLC6A3 10/10 genotype category, the risk of schizophrenia was halved among those with 9/10 [OR = 0.51 (95% CI = 0.30–0.89), p = 0.017]. This protective effect was only present in combination with DRD3 Ser/Ser genotype because of the significant interaction between 9/10 and both Ser/Gly [OR = 2.45 (95% CI = 1.16–5.17), p = 0.019] and Gly/Gly [OR = 3.80 (95% CI = 1.24–11.63), p = 0.019].

Conclusions

This study provides evidence that a genetic variant in the DRD2 gene and possible interaction between DRD3 and SLC6A3 genes are associated with schizophrenia. These findings warrant examination in replication studies.     

Polymorphisms of RANTES and IL-4 Genes in Cerebral Infarction

Chemoattractant peptides (chemokines) and cytokines have been shown to play a key role in the inflammatory development and progression of cerebrovascular disease. The effect of polymorphisms in regulated upon activation, normal T cells expressed, and secreted (RANTES) and interleukin-4 (IL-4) genes on cerebral infarction (CI) is evaluated in this study. Patients with CI (n = 320) and healthy controls (n = 481) were genotyped for RANTES-403 and IL-4 variable number of tandem repeat (VNTR) polymorphisms using polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism. A significant difference was observed between the CI group and controls in subjects with the RANTES AA genotype in IL-4 A3− carriers (18.6% vs. 13.1%, P = 0.035, odds ratio = 1.5, 95% confidence interval = 1.03–2.25). These findings suggest that the RANTES G-403A allele increased the relative risk for CI in the subjects without the IL-4 VNTR allele 3.     

The magnificent seven: A quantitative review of dopamine receptor d4 and its association with child behavior

A large volume of behavioral research has explored the variable number of tandem repeat (VNTR) polymorphism on the dopamine receptor D4 gene (DRD4). However, findings are inconsistent and there is no agreement about what constitutes “functional” and “less functional” variants at this locus. First, we systematically review studies exploring biological differences between DRD4 VNTRs (k = 21). Second, we systematically review studies relating DRD4 variation to behavioral traits in population-based, non-clinical samples of children and adolescents (k = 46; N = 13,195), highlighting the various genotypic classifications previously used. Third, we use meta-analyses to examine associations of DRD4 VNTRs with five broadly-defined behavioral outcomes (externalizing and attention problems, executive function, social/emotional development, and “reactive” temperament). We identify a significant association of “longer” DRD4 variants with lower levels of executive function and social/emotional development, but not independent of the choice of genotypic classification. We suggest that until the functionality of DRD4 VNTRs is established, researchers should report all genotypic classifications to ensure full transparency and allow for further meta-analytic work.     

The 1674+11C>T polymorphism of CHRNA4 is associated with juvenile myoclonic epilepsy

The α4 subunit gene (CHRNA4) of the neuronal nicotinic acetylcholine receptor (nAChR), linked to an idiopathic partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), may also play a key role in the development of the idiopathic generalized epilepsy syndrome (IGE), juvenile myoclonic epilepsy (JME). This study was designed to explore an association of four polymorphisms of the CHRNA4 with JME in Polish children and young patients. The study included 92 JME patients and 222 unrelated healthy individuals. In each group the frequencies of the CHRNA4 c.555C>T, c.594C>T, 1674⁺¹¹C>T, and 1674⁺¹⁴A>G polymorphisms were determined using PCR-RFLP analyses. An association between the 1674⁺¹¹C>T polymorphism of the CHRNA4 and JME was evidenced. Allele T (the risk factor) appeared with a significantly higher frequency in the JME patients than in the controls (p = 0.0299). The patients harboring the 1674⁺¹¹CT+TT genotypes showed an increased risk of JME (CT+TT versus CC: OR = 1.925; 95% CI = 1.021–3.629; p = 0.0408). No association was found for the other CHRNA4 polymorphisms tested. The CHRNA4 1674⁺¹¹C>T polymorphism may be a susceptibility factor for epilepsy, and its higher frequency in patients with juvenile myoclonic epilepsy suggests that the CHRNA4 may be one of the candidate genes for this epileptic syndrome.     

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.     

Gender-specific expression of the DRD4 gene on adolescent delinquency,anger and thrill seeking

The present study investigated gender differences in the associations between the DRD4 variable number tandem repeat (VNTR) polymorphism and adolescent delinquency, short temper and thrill seeking. We also explored whether the gender-specific expression of the DRD4 can be explained by gender differences in the exposure to psychosocial risks, such as poor parent–child relationship. Participants were 263 14- to 17-year olds (50% males) living in Russia. DNA was extracted from saliva samples and the VNTR DRD4 polymorphisms were genotyped using polymerase chain reaction. Participants reported on the extent of their delinquent behaviour, short temper, thrill seeking and exposure to psychosocial risk (i.e. poor parental monitoring of adolescent behaviour, exposure to violence and peer delinquency). Compared to individuals with the 4/4 genotype, males, but not females, with the 7-repeat allele (7R) had significantly higher delinquency, short temper and thrill seeking. This interaction effect, however, was completely explained by males’ higher exposure to psychosocial risk factors. When parental monitoring of youths’ activities and youth exposure to violence were included in the model, the 7R × gender interaction was no longer significant. Thus, social context plays an important role in explaining gender-specific phenotypic expression of the DRD4 gene.     

Cognitive and emotional processing associated with the Season of Birth and dopamine D4 receptor gene

The 7-repeats variant of the dopamine D4 receptor (7R) VNTR polymorphism has been associated with higher novelty seeking (NS) and disadvantageous decision making in the Iowa Gambling Task (IGT). Season of Birth (SOB) is a significant determinant of NS. SOB and L-DRD4 genetic polymorphism may independently and interactively influence similar behaviors through their common effects on the dopaminergic system. Two hundred and twenty-seven healthy males grouped in summer-born/4-repeats (4R) (n = 75), winter-born/4R (n = 90), summer-born/7R (n = 31) and winter-born/7R (n = 31) groups, completed multimodal assessment for personality, planning for problem solving and decision making. Winter-born/7R subjects had significantly worse IGT performance throughout the task compared to 4R individuals, while summer-born 7R subjects had intermediate, although not significantly different performance. Moreover, winter-born/7R subjects had increased behavioral approach to reward without parallel reduction in sensitivity to fear or to social approval cues. The DRD4-by-SOB groups did not differ in planning for problem solving. These results suggest that a DRD4-by-SOB interaction is associated with increased behavioral approach to reward and risk taking but efficient problem solving. In addition, these results further support the hypothesis that SOB modifies the behavioral expression of dopaminergic genetic polymorphism. SOB should be included in future studies of risky behaviors and behavioral genetic studies of the dopamine system.     

High Association of IL-4 Gene Intron 3 VNTR Polymorphism with Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is a common disease. It is one of the late complications of diabetes mellitus. DPN can lower the quality of life by causing severe painful clinic symptoms. The aim of this study is to evaluate interleukin (IL)-4 gene variable number of tandem repeat (VNTR) polymorphism on DPN in Turkish population. Two hundred and twenty-seven DPN patients and 241 controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction analyses for the IL-4 gene intron 3 VNTR polymorphism. The distribution of genotype frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between DPN patients and control group (p?=?0.001). The frequency of P1 and P2 alleles was statistically different between DPN patients and control group (p?=?0.00009). The results of this study suggested that intron 3 VNTR polymorphism of the IL-4 gene plays an important role in the occurrence of DPN in the Turkish population.