OBJECTIVE: It is suggested that disturbance of dopaminergic system might be related to the possible mechanism of social phobia. The aim of this study was to investigate the possible association of DRD2 TaqI polymorphism and social phobia. METHOD: Fifty-one patients with social phobia and 200 comparison subjects were tested for DRD2 TaqI A polymorphism. The severity of social phobic symptoms was measured by self-report version of the Liebowitz Social Anxiety Scale(LSAS-SR) and Hamilton anxiety scale(HAM-A). RESULTS: There was no signigicant difference in the genotype, allele frequency, A1 carrier frequency, and heterozygote frequency DRD2 TaqI A polymorphism between the social phobia patients and the control groups. However, we found significant decrease in somatic anxiety of the HAM-A in the patients having A2A2 homozygotes(p=0.014). In addition, patients having A1A2 heterozygotes showed more anxiety in two subscales(p=0.042 in anxiety, p=0.019 in performance) of the LSAS-SR. CONCLUSION: These results suggest that DRD2 A2 homozygote might have a protective role against somatic anxiety, and molecular heterosis of DRD2 TaqI A polymorphism might be related with more severe anxiety in social phobia.
Anxiety ; Dopamine* ; Gene Frequency ; Genotype ; Heterozygote ; Homozygote ; Humans ; Hybrid Vigor ; Phobic Disorders* ; Receptors, Dopamine D2*

OBJECTIVE: This study was to examine the effects of DRD2 TaqI A polymorphism on the smoking in Koreans. Also this study examined molecular heterosis and gender difference in the genetic effect of cigarette smoking. METHODS: DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 187 healthy individuals including 94 smokers and 93 non-smokers, RESULTS: Among the total subjects, the smokers were not significantly different from the non-smokers in respect to the frequency and prevalence of A1 allele, the genotype distribution, or the frequency of heterozygotes. Separating the subjects by gender, however, in male subjects smokers showed a significantly higher frequency (p=0.049) and prevalence of A1 allele (p=0.016) than non-smokers. Also, genotype distribution (p=0.055) and frequency of heterozygotes (p=0.058) of smokers showed some different distributions, but there were no significant statistical difference. In contrast, female subjects showed significant difference between smokers and non-smokers in the comparison of frequency of heterozygotes (p=0.018), but not in the comparison of the frequency (p=0.582) and prevalence (p=0.082) of A1 allele and genotype distribution (p=0.060). CONCLUSION: No significant difference between smokers and non-smokers in the genotype distributions of the total sample could be explained by the reciprocal effects of gender difference in the genetic effect of DRD2 A1 allele of the smoking. Our findings support gender difference and molecular heterosis at the DRD2 gene effects of smoking.
Alleles ; DNA ; Dopamine* ; Female ; Genotype ; Heterozygote ; Humans ; Hybrid Vigor ; Male ; Polymorphism, Restriction Fragment Length ; Prevalence ; Receptors, Dopamine D2* ; Smoke ; Smoking* ; Tobacco Products*

Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic effects on specific depressive symptom-clusters.
Animals ; Asian Continental Ancestry Group ; Brain-Derived Neurotrophic Factor ; Depression ; Depressive Disorder, Major ; Down-Regulation ; Haplotypes ; Homozygote ; Humans ; Hybrid Vigor ; Neuronal Plasticity ; Polymorphism, Genetic

OBJECTIVE: The authors examined the genetic effect of DRD2 Taq I polymorphism to the smoking in the Korean schizophrenics. Also this study examined molecular heterosis and gender difference in the genetic effect to smoking in schizophrenics. METHODS: The study subjects were composed of 167 schizophrenic patients, 96 smokers and 71 non-smokers. DRD2 Taq I RFLP genotyping was carried out with DNA extracted from subjects' blood samples. RESULTS: Among the total schizophrenics, the smokers were not significantly different from the non-smokers in respect to the frequency and prevalence of A1 allele, the genotype distribution, or frequency of heterozygotes. In male schizophrenics, genotype distribution of smoking patients differed significantly from non-smoking patients(p=0.010), with a higher prevalence of A1 allele (p=0.020) and frequency of heterozygotes(p=0.005). In male schizophrenics, A1A2 heterozygotes showed significantly higher smoking rate than A1A1 or A2A2 homozygotes and non-smokers were deficient in heterozygotes. The deviation from Hardy-Weinberg expectations was observed in male and female non-smokers with opposite directions. Moreover, highly significant differences were seen between male and female non-smokers in A1 prevalence(p=0.001), genotype distribution(p<0.00011), and frequency of heterozygotes(p<0.00003). CONCLUSION: No significant difference between smokers and non-smokers in the genotype distributions of the total sample could be explained by the gender difference in the genetic effect of DRD2 A1 allele to the smoking with opposite directions. Our findings support molecular heterosis at the DRD2 gene.
Alleles ; DNA ; Dopamine* ; Female ; Genotype ; Heterozygote ; Homozygote ; Humans ; Hybrid Vigor ; Male ; Nicotine ; Polymorphism, Restriction Fragment Length ; Prevalence ; Receptors, Dopamine D2* ; Schizophrenia* ; Smoke* ; Smoking*