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Biomedical subjects

Chen-Jee Hong

Publications and source records attributed to Chen-Jee Hong.

At least 19 recordsLinked to original sources

Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression.

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE epsilon4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE epsilon4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.

Aged↗

Family-based association study between G72/G30 genetic polymorphism and schizophrenia.

Genetic variations in G72/G30 have been reported to be associated with schizophrenia and bipolar disorders in several case-control studies. This gene is located in a genomic region known to contain susceptibility genes for schizophrenia. As case-control studies carry an increased risk of confounding through population stratification, we investigate whether the rs947267 (A/C) polymorphism is associated with schizophrenia in a family-based association study. This polymorphism is located within the G72/G30 gene and has been previously associated with bipolar disorders. The sample consisted of a total of 216 Chinese families that included an affected offspring and parents. Transmission disequilibrium analysis revealed a significant association between the G72/G30 rs947267 polymorphism and schizophrenia (P=0.016), with the A allele more commonly transmitted to patients. Further analysis stratified by sex showed that the A allele was significantly more overtransmitted than nontransmitted in the trios of male probands (P=0.031), but not in the trios of female probands. Our family-based association study supports the suggestion that the G72/G30 gene may be implicated in susceptibility to schizophrenia and there may be an interaction between this gene and sex in the pathogenesis of schizophrenia.

Adult↗

Association study of two serotonin 1A receptor gene polymorphisms and fluoxetine treatment response in Chinese major depressive disorders.

The firing rate of dorsal raphe serotonergic neurons is modulated by somatodendritic 5-hydroxytryptamine 1A (HTR1A) autoreceptors. Evidence from animal and clinical studies has suggested that desensitization of HTR1A is implicated in the antidepressant therapeutic mechanism of selective serotonin reuptake inhibitors (SSRIs). Recent studies, including our recent findings, have reported that a functional HTR1A C-1019G polymorphism in the promoter region, as well as a nonsynonymous polymorphism, Gly272Asp, may be associated with SSRI pharmacogenetics. In this study, we tested whether Gly272Asp genetic variants are related to a 4-week fluoxetine antidepressant effect in 222 Chinese major depressive patients. We also tested the linkage disequilibrium (LD) measurement between HTR1A Gly272Asp and C-1019G polymorphisms, and haplotype analysis was conducted to assess the association between the two markers within the HTR1A gene and fluoxetine antidepressant response. The results show that the HTR1A Gly272Asp polymorphism was not associated with fluoxetine therapeutic response. The two markers are in strong LD and the HTR1A haplotype of the two polymorphisms is associated with fluoxetine therapeutic response. This association is gender-specific and mostly arises from the effect of HTR1A C-1019G polymorphism: female patients with -1019C/C genotype showed a better response than -1019G carriers. These findings need to be confirmed in other ethnic populations.

Adult↗

The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer's disease in a chinese population.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may represent a candidate gene conferring susceptibility to Alzheimer's disease (AD). This is because it has an important role in neuronal survival, and a decreased central level of BDNF is observed in AD. Some previous studies, though not all, have demonstrated that BDNF C270T polymorphisms might be associated with AD susceptibility. We examined the association of the C270T polymorphisms with sporadic AD in a Chinese cohort of 175 AD patients and 189 controls. We also tested BDNF Val66Met-C270T haplotypes for an interaction with the apolipoprotein E upsilon4 (APOE4) allele in AD. The results showed that the frequency of the 66Val allele was significantly lower in AD than controls (p = 0.031), but no significant difference in C270T allele or genotype frequencies was observed between AD cases and controls. Global case-control haplotype analysis showed that there is significant difference in haplotype distribution between both groups (p = 0.033). Stratification of the data according to the APOE status showed that in APOE4 allele bearers there was no significant difference in the frequency of haplotype 66Val-270C between AD and controls (p = 0.125), although there was a significant difference between the two groups in non-APOE4 carriers (p = 0.002). These results suggest that BDNF genetic variation may possibly affect the risk for AD, particularly in subjects who are negative for APOE4.

Alleles↗

Association study of adenosine A2a receptor (1976C>T) genetic polymorphism and mood disorders and age of onset.

Evidence suggests that the adenosine A2a receptor (A2aAR) may be implicated in the pathogenesis of mood disorders. We tested the hypothesis that the A2aAR 1976C>T genetic variant confers susceptibility to mood disorders by comparing 192 mood disorder patients and 216 normal controls. The distribution of the A2aAR genotypes and alleles did not differ significantly comparing the two groups, suggesting that it is unlikely that the A2aAR 1976C>T polymorphism plays a major role in the development of mood disorders.

Age of Onset↗

Polymorphisms in glycine transporter with schizophrenia.

Glycine acts as an obligatory co-agonist with glutamate on N-methyl-D-aspartate (NMDA) receptors. Brain glycine availability is determined by glycine transporters (GlyT1 or SLC6A9), which mediate glycine reuptake into nerve terminals. Since hypofunction of NMDA receptors has been implicated in the pathophysiology of schizophrenia, this study tests the hypothesis that GlyT1 genetic variants confer susceptibility to schizophrenia. Four GlyT1 polymorphisms were studied in a sample population of 249 people with schizophrenia and 210 normal controls. One polymorphism (rs16831541) was not informative in our Chinese population while the other three polymorphisms (rs1766967, rs2248632 and rs2248253) were analysed with chi-square tests and haplotype analysis. Significant linkage disequilibrium was obtained among the three polymorphisms. Neither single marker nor haplotype analysis revealed an association between variants at the GlyT1 locus and schizophrenia, suggesting that it is unlikely that the GlyT1 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia in the Chinese population. Further studies with other GIyT1 variants, relating either to schizophrenia, psychotic symptoms or to therapeutic response in schizophrenia, are suggested.

Adult↗

Association study of androgen receptor CAG repeat polymorphism and male violent criminal activity.

Androgens exert their effects primarily by stimulating androgen receptors (ARs) and androgen activity has been implicated in antisocial or violent criminal behaviour. Exon 1 of the AR gene contains a highly polymorphic glutamine (CAG) repeat sequence. We tested the hypothesis that shorter AR CAG repeat polymorphisms, which have a greater AR gene expression, are related to violent criminal activity in Chinese males using a sample of 146 extremely violent criminals and 108 normal controls. The results show no association between the AR repeat length and violent convicts, although we found that there are more violent-criminal cases than control cases with the shorter (<17) AR gene trinucleotide repeat polymorphisms (7.5% vs. 1.9%; P=0.047). No correlation was found between the AR CAG repeat length and the first criminal record age in the violent-criminal group. The mean AR repeat length is not significantly different between substance dependence cases and antisocial personality disorder diagnosis in the violent criminals and normal controls. Our findings suggest that the AR CAG repeat polymorphism does not play a major role in the susceptibility of male violent criminal activity.

Asian People↗

The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression.

Brain-derived neurotrophic-factor (BDNF), the most abundant of the neurotrophins in the brain, has been implicated in both major depression and cognitive function. This study examines the association between the BDNF-gene Val66Met polymorphism and depression susceptibility and severity, age-of-onset, cognitive function and suicidal attempt history in an elderly Chinese sample population. We genotyped the BDNF-gene Val66Met polymorphism in 110 elderly inpatients diagnosed with major depression and 171 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. Suicide attempt history and age-of-onset of depression were evaluated by interview and medical record. The BDNF Val66Met genotype distribution was significantly different between depressed patients and control subjects (P=0.003) and there was a significant excess of Met allele in the depressed patients compared to the control group (P=0.001). The BDNF polymorphism did not affect age-of-onset, depression severity, cognitive function or suicidal attempt history. The results suggest that the BDNF Val66Met polymorphism is a relevant risk factor for geriatric depression.

Aged↗

Interleukin-6 genetic polymorphism and Chinese major depression.

BACKGROUND: It has been reported that serum concentrations of interleukin-6 (IL-6), a pro-inflammatory cytokine, were significantly higher in major depressive disorder (MDD). OBJECTIVES: The aim of the present study was to examine whether the IL-6 genetic variant confers susceptibility to MDD. METHODS: We genotyped a functional polymorphism in the promoter region (position -634) of the IL-6 gene in a sample of 257 MDD patients and 105 normal controls. RESULTS: No significant differences were demonstrated for the genotype or allele frequency of the IL-6 polymorphism when comparing the MDD and control groups. CONCLUSIONS: Our findings suggested that the investigated IL-6 polymorphism does not affect MDD susceptibility. We propose that other genetic variations of IL-6, relating either to MDD or to the clinical manifestations of MDD, may need further investigation.

Adult↗

Distribution of androgen receptor CAG repeat polymorphism in Chinese schizophrenia and its correlation with age at onset.

The action of androgens is mediated by the androgen receptors (ARs), which are located throughout the brain. The AR gene is implicated in the pathogenesis of schizophrenia because male siblings with schizophrenia share alleles at this gene at a rate higher than chance predicts, and differences in sex hormone function may explain the gender difference in schizophrenic manifestations. Since the shorter alleles of the AR CAG repeat polymorphism are associated with increased gene expression, we tested the hypothesis that the AR CAG repeat variant confers susceptibility to schizophrenia using a sample of 225 people with schizophrenia and 247 normal controls. Using the median AR repeat length in the normal group as the arbitrary cut-off point (<24 and >25 CAG repeats), the results show no association between the AR repeat length and schizophrenia in either sex. Furthermore. AR CAG repeat length did not affect the age of symptom onset in the schizophrenic population. Our findings suggest that it is unlikely that the AR CAG repeat polymorphism plays a major role in the pathogenesis of schizophrenia. Nevertheless, given that androgens affect cognitive function, violent behavior and mood, the effect of the AR CAG polymorphism on the clinical manifestations of schizophrenia may warrant further exploration.

Adult↗

Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males.

Data from animal studies and from genetic scans in humans suggest that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be involved in the mechanisms underlying substance abuse. The present study tested the hypothesis that the BDNF-gene Val66Met polymorphism is associated with substance abuse. We studied this polymorphism in 103 methamphetamine- and 200 heroin-dependent cases and 122 normal controls. We also considered the association of this polymorphism with age of onset of substance abuse in the heroin-dependent cases. Significant differences in BDNF Val66Met genotype distribution were found between subjects dependent on methamphetamine (P = 0.046) or heroin (P = 0.045) and controls, suggesting that the lower 66Met carrier frequency is associated with substance abuse. Furthermore, in the heroin-dependent group, the Val/Val homozygotes had a later onset of substance abuse compared with the Met allele carriers. The results suggest that the BDNF Val66Met polymorphism or a nearby locus may be involved in the pathogenesis of substance abuse. Our findings support previous genetic scan results showing that BDNF may contribute to substance abuse vulnerability.

Amino Acid Substitution↗

Association study of a functional MAOA-uVNTR gene polymorphism and personality traits in Chinese young females.

Monoamine oxidase A (MAOA), a mitochondrial outer membrane enzyme, degrades biogenic amines including norepinephrine, dopamine and serotonin, which have been implicated in the expression of personality traits. We tested the associations between functional MAOA-uVNTR genetic variants and personality traits in a cohort of 370 healthy young Chinese females. Subjects who were homozygous for the 4-repeat allele of the MAOA-uVNTR gene tended to have a higher total score on the Harm Avoidance (HA) dimension of the Tridimensional Personality Questionnaire (TPQ) (p = 0.056), and had a significantly higher score on subdimension 4 of HA (p = 0.020) compared with the 3-repeat carriers. No significant association was demonstrated for MAOA-uVNTR polymorphism and the other two dimensions (Novelty Seeking and Reward Dependence) of TPQ. These results suggest that genetic variants of the MAOA gene may play a role in HA, but not in Novelty Seeking or Reward Dependence.

Adult↗

Association study of a functional MAOA-uVNTR gene polymorphism and cognitive function in healthy females.

Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in the degradation of dopamine, serotonin and norepinephrine and these neurotransmitters are hypothesized to be involved in the cognitive function of humans. This study of a cohort of 191 healthy young Chinese females attempts to utilize the intelligence quotient (IQ), Wisconsin Card Sorting Test (WCST) and P300 event-related potentials as cognitive assessments for testing the relationship between the polymorphism with a variable number of tandem repeats (VNTR) in the upstream regulatory region (MAOA-uVNTR) and cognition. The results demonstrate that subjects bearing the 4/4-repeat genotype have a significantly higher full IQ than subjects bearing the 3/3-repeat genotype. However, there is no significant association between this MAOA-uVNTR polymorphism and the WCST and P300. Our study shows that the MAOA-uVNTR genetic polymorphism plays a role in the IQ; however, this may be a chance finding as the result was negative after using the Bonferroni adjustment. Therefore, we suggest that our study should be replicated and that the testing method, sex, disease and ethnicity should also be considered in future studies.

Adult↗

Effects of subchronic clozapine administration on serum glucose, cholesterol and triglyceride levels, and body weight in male BALB/c mice.

Atypical antipsychotics, like clozapine, have fewer extrapyramidal side effects compared with typical antipsychotics, however, such treatment is associated with several adverse metabolic effects such as weight gain, hyperglycemia and hyperlipidemia in patients with schizophrenia. In this study, we investigated the effects of 30-day clozapine treatment on weight change, and serum fasting glucose, cholesterol and triglyceride levels in male BALB/c mice. The results demonstrate that 10.0 mg/kg clozapine group gained significantly less weight but had higher cholesterol compared with controls and the 2.0 mg/kg clozapine group. Our findings indicate the possibility of using mice to study the mechanisms of body weight change and lipid dysregulations induced by clozapine.

Animals↗

A study of the association of (Val66Met) polymorphism in the brain-derived neurotrophic factor gene with alcohol dependence and extreme violence in Chinese males.

From studies of genetic-knockout animals, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth-factor family, has been implicated in both alcohol preference and aggressive behaviour. To test whether a BDNF genetic variant may be associated with alcohol-dependent and violent behaviours, we studied Val66Met polymorphism of the BDNF-gene in 110 cases of alcohol-dependence, in 134 extremely violent convicts, and in 149 individuals without psychosis or mood disorders. We also examined the association of this polymorphism with antisocial personality disorder comorbidity in the extremely violent convicts. The results showed that the genotype and allele frequencies for Val66Met polymorphism at the BDNF-gene site did not differ among the three groups. Furthermore, it was not demonstrated that this polymorphism is associated with antisocial personality disorder comorbidity in the extremely violent convicts. Based on these findings, it seems reasonable to suggest that this BDNF-gene Val66Met polymorphism is unlikely to play a major role in the genetic susceptibility to the traits of alcohol-dependence or violence proneness.

Adult↗

Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response.

Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of biogenic amines, may be implicated in the pathogenesis of major depressive disorder (MDD) and be related to the therapeutic effects of antidepressants. To elucidate a genetic predisposition of MDD, we studied a variable-number-tandem-repeat (VNTR) polymorphism in the promoter region of the MAOA gene in a Chinese population of 230 MDD patients and 217 controls. We also examined the association of this polymorphism and antidepressant therapeutic response in the MDD patients who underwent a 4-week fluoxetine treatment. Our results showed a significantly increased frequency of 4-repeat (4R) allele in MDD patients, especially in the female population. Furthermore, MDD female patients who were 3R homozygotes had a significantly better response to 4-week fluoxetine treatment when compared to 4R carriers (p=0.024), but there was a nonsignificant difference found in male patients (p=0.081). Since the 4R allele transcribed 2-10 times more efficiently than those with 3R allele, our findings suggest that the MAOA-uVNTR may be involved in the pathogenesis of MDD and the antidepressant therapeutic mechanisms in Chinese population, and that there may be a gender effect in this association.

Adolescent↗