Search PubMed⌕ Search

Biomedical subjects

C J Hong

Publications and source records attributed to C J Hong.

At least 55 records · Page 3Linked to original sources

Association analysis of the 5-HT6 receptor polymorphism C267T in Alzheimer's disease.

Serotonergic dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD). This association study explores whether the serotonin 6 receptor (5-HT6) polymorphism (C267T) is a susceptibility factor for AD. Statistical analysis showed a significant difference in the genotype and gene frequencies between the AD group and the normal controls (P = 0.006; and P = 0.023, respectively). These findings indicate that the 267C allele of the 5-HT6 gene is a risk factor for AD.

Aged↗

ApoE genotype in relation to AD and cholesterol: a study of 2,326 Chinese adults.

OBJECTIVE: To calculate the frequencies of apolipoprotein E (apoE) alleles in a large Chinese community sample and to compare the serum cholesterol levels of epsilon2, epsilon3, and epsilon4 carriers. BACKGROUND: In comparison with Western populations, a lower frequency of the apoE epsilon4 allele among the Chinese has been proposed as one factor for the lower prevalence of AD found in Chinese populations, but there are insufficient Chinese data on epsilon4 frequency that are based on large community samples. In addition, although Western studies have repeatedly found a lower cholesterol level in epsilon2 carriers and a higher cholesterol level in epsilon4 carriers in comparison with epsilon3 homozygotes, two Chinese studies have yielded inconsistent findings between them. METHODS: During the incidence phase of an epidemiologic survey of several neurologic disorders in a Chinese community, the authors took blood samples from 2,326 participants to determine the apoE genotypes and to measure cholesterol levels. RESULTS: The allelic frequencies of epsilon2, epsilon3, and epsilon4 were 11.8%, 76.4%, and 11.8% among 17 AD patients, and 7.8%, 84.1%, and 8.1% for the entire sample. The mean cholesterol level of the epsilon2 carriers was significantly lower, and that of the epsilon4 carriers significantly higher, than that of the epsilon3 homozygotes. CONCLUSIONS: The obtained epsilon4 rate of 8.1% is lower than most of the Western findings, and this may account in part for the lower prevalence of AD found among the Chinese. The associations between the apoE genotype and serum cholesterol level are similar between Chinese and white populations.

Aged↗

Association study of serotonin-6 receptor variant (C267T) with schizophrenia and aggressive behavior.

The relative abundance of serotonin type 6 receptors (5-HT6) in some limbic regions and the high affinity of some antipsychotics to 5-HT6 receptors suggest that they might be involved in the pathogenesis of schizophrenic disorders. In a population-based association study, we tested the hypothesis that the allelic variant, C267T, of the human 5-HT6 gene confers susceptibility to schizophrenic disorders and associated aggressive behavior. We genotyped 5-HT6 receptors in 186 patients with schizophrenic disorders and 163 controls. The results demonstrated no significant difference in genotype or allele frequencies between patients with or without aggressive behaviors. However, genotype distribution was significantly different between schizophrenic patients and control subjects. This suggests that the 5-HT6 gene may play a role in the pathogenesis of schizophrenic disorders.

Adult↗

Serotonin-6 receptor variant (C267T) and clinical response to clozapine.

Clozapine is an effective atypical antipsychotic that has high affinity for serotonin type 6 receptors (5HT6). We tested the hypothesis that clinical response to clozapine in patients refractory to typical antipsychotic treatment is related to the genetic variant (C267T) of the 5HT6 receptors. Ninety-nine schizophrenic patients with a history of non-response to typical antipsychotics were included in the study. The results demonstrated a modest but significant relationship between presence of the variant of the 5HT6 receptors and the response to clozapine in these patients. Patients with homogenous 267T/T genotype had a better response than other patients. Although replication is required, these results suggest that the 5HT6 receptor C267T polymorphism may be involved in clozapine response, especially in patients with anxious or depressed symptoms.

Antipsychotic Agents↗

No evidence for association of serotonin-2A receptor variant (102T/C) with schizophrenia or clozapine response in a Chinese population.

The serotonin hypothesis in schizophrenia had regained interest with the superior efficacy of clozapine in the refractory schizophrenic patients. Among the serotonin receptors, the serotonin 2A (5HT2A) receptor subtype is the most widely studied. Previous studies on the association between a silent mutation polymorphism of the 5HT2A gene (102T/C) and schizophrenia or clozapine response have yielded conflicting findings. Therefore, we investigated whether these genetic variants of the 5HT2A receptor are associated with schizophrenia or with response to clozapine treatment in a Chinese population. Ninety-seven schizophrenic patients and 101 control subjects were included in the study. The receptor variants were found at similar frequencies in schizophrenic patients and healthy control subjects. Also, we did not find the variants to influence the response to clozapine in schizophrenic patients. We suggest that the assessment method of clozapine response and the ethnicity may influence the result.

Adult↗

Apolipoprotein E genotype and schizophrenia.

Schizophrenic disorders are complex genetic disorders and may involve multiple genes of small effect. The presence of apolipoprotein E (apoE) is associated with several neuropsychiatric disorders. Previous studies on apoE genotype distribution in schizophrenia have reported conflicting findings. We studied the genotype frequencies in a large group of schizophrenic patients. The genotype distribution was significantly different between the schizophrenic patients and the control subjects. Persons who were sigma3 carriers have an increased risk of schizophrenia. This result suggests that apoE isoforms may play a functional role in the pathogenesis of schizophrenic disorders. Some possible mechanisms regarding the effect of apoE on the development of schizophrenia are discussed.

Aging↗

No association between alpha-1-antichymotrypsin polymorphism and Alzheimer's disease in Chinese.

A recent observation has shown that a common polymorphism in the alpha1-antichymotrypsin (ACT) confers a significant risk for Alzheimer's disease (AD). Furthermore, the apolipoprotein E epsilon4 allele (APOE*4) effect associated with AD risk is modified by the ACT polymorphisms. To evaluate the role of ACT polymorphism in AD, we conducted an association study of ACT polymorphisms in Chinese AD patients and normal controls. We found that the ACT polymorphism had no effect on the development of AD either alone or in combination with the APOE*4 allele.

Aged↗

Alpha-1-antichymotrypsin polymorphism in schizophrenia: frequency, age at onset and cognitive function.

A common polymorphism in the alpha1-antichymotrypsin (ACT) gene is associated with Alzheimer's disease. ACT is also a trophic factor in the hippocampal neurons. In order to examine if the ACT gene plays a role in the pathogenesis of schizophrenic disorders, patients (n = 175) and control subjects (n = 114) were genotyped for ACT. We also investigated the relationship between genotypes and patients' cognitive function as evaluated by the Clinical Dementia Rating Scale and the Mini-Mental State Examination. The results demonstrated no association between schizophrenia and/or cognitive deficit in schizophrenia and ACT polymorphism. The data suggest that the ACT gene is not of major importance for the genesis of schizophrenia. Further studies measuring ACT expression as messenger RNA or serum ACT level may help to exclude the role of ACT in the pathogenesis of schizophrenia.

Adult↗

Dopamine D4 receptor gene polymorphisms and neuroleptic response in schizophrenia.

BACKGROUND: Dopamine D4 receptor (DRD4) gene polymorphisms are associated with various pharmacologic activities. This study investigated whether polymorphisms of 48-bp tandem repeats in the exon 3 of the DRD4 gene are related to neuroleptic response. METHODS: The neuroleptic response at the acute stage of schizophrenia was assessed in 80 (48 men, 32 women) schizophrenic patients. The negative symptoms at remission were also rated. DRD4 genotype was established using the polymerase chain reaction. Patients with genotypes containing an allele with only two repeats (2-2, 2-3, 2-4, 2-6) were assigned to group I (n = 38). Those homozygous for four 48-bp repeats were assigned to group II (n = 42). RESULTS: Thirteen (34.2%) of the 38 group I subjects and 26 (61.9%) of the 42 group II subjects had good neuroleptic response during acute stage treatment (chi 2 6.12, df = 1, p < .02). In remission, the rates of negative symptoms of blunt affect, avolition, and global negative rating were higher in group I than in group II. This was more prominent in men than in women. CONCLUSIONS: The presence of homozygous four 48-bp repeats in both alleles in exon 3 of the DRD4 gene is associated with good neuroleptic response during acute treatment, and with a lower prevalence of negative symptoms at remission, especially in male schizophrenic patients.

Adult↗

Twelve-nucleotide repeat polymorphism of D4 dopamine receptor gene in Chinese familial schizophrenic patients.

BACKGROUND: Disturbances in dopaminergic transmission have been implicated in the etiology of schizophrenia. Catalano et al reported an association between delusional disorder and the number of a 12-nucleotide (bp) repeat sequence in the first exon of dopamine D4 receptor gene (DRD4), which indicated a possible role of this polymorphism in the pathogenesis of psychotic disorders. METHODS: DNA of 42 Chinese controls, 50 sporadic schizophrenic patients, and 30 familial schizophrenic probands were collected. Genotype of the 12-bp repeat polymorphism of DRD4 was determined with polymerase chain reaction and agarose gel electrophoresis. Genotypic and allelic frequencies were compared among the three groups using the chi-square test. RESULTS: Forty-three (86%) sporadic schizophrenic patients, 25 (83.3%) familial schizophrenic probands, and 35 (83.3%) controls were A1 (two 12-bp repeat) homozygotes. One (2.0%) sporadic schizophrenic and 1 familial schizophrenic patient were A2 (one 12-bp repeat) homozygotes. There was no significant difference in allelic and genotypic distributions among the three groups. CONCLUSIONS: The present data do not support an association between schizophrenia and any specific allele of the 12-bp repeat polymorphism of DRD4. Significance of familial/sporadic division of schizophrenia cannot be supported regarding this repeat polymorphism.

Adult↗

Dopamine D4 receptor variants in Chinese sporadic and familial schizophrenics.

Variation in the number of tandem repeats of a 48 base pair (bp) unit was found in the gene of the dopamine D4 receptor (DRD4). The number of repetitions of the 48bp unit was shown to influence the binding of clozapine, which suggests that different alleles may function differently in vivo and affect the pathogenesis of schizophrenia. Genotypes of DRD4 polymorphism were analyzed for 47 schizophrenic probands who had at least one living sibling with a diagnosis of schizophrenia, 35 unaffected siblings of the schizophrenic proband, 42 sporadic schizophrenic patients, and 43 healthy controls without a family history of psychosis. There was no significant difference in genotypic or allelic distributions among the four groups. Significant differences in the frequencies of two- and seven-repeats alleles between the Chinese and Caucasians controls were noted. The present study did not support that a particular allele or genotype of the 48bp-repeat of DRD4 was associated with schizophrenia.

Adult↗

Prevalence of apolipoprotein E genotypes in ischaemic cerebrovascular disease in end-stage renal disease patients.

BACKGROUND: Several studies have demonstrated that atherosclerotic complications are the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients on dialysis. The allele epsilon 4 of apolipoprotein E (ApoE) gene has been associated with an increased risk for ischaemic cerebrovascular disease (ICVD) in general populations in recent preliminary cross-sectional studies. METHODS: The aim of our study was to prospectively investigate the risk of ischaemic cerebrovascular disease with respect to the presence of Apo epsilon 4 allele in 157 Chinese uraemic patients. RESULTS: During the 2 year follow-up, the incidence of stroke was 6.4% and the cumulative occurrence of ischaemic cerebrovascular disease was 9.6%. Further analysis showed that the cumulative occurrence of ischaemic cerebrovascular disease was 5.6% in subjects with no ApoE epsilon 4 allele and 36.8% in those with one or two ApoE epsilon 4 alleles. Univariate analysis showed that the prevalence of ischaemic cerebrovascular disease was significantly higher in the subjects with ApoE epsilon 4 allele. The mean ApoA1 plasma concentrations was significantly lower in those with ApoE epsilon 4 allele. A stepwise regression analysis showed that the presence of stroke was significantly related to the ApoE epsilon 4 genotype (P < 0.001). CONCLUSIONS: The ApoE epsilon 4 allele can be regarded as an important risk factor for ischaemic cerebrovascular disease in uraemic patients.

Adult↗

A double-blind comparative study of clozapine versus chlorpromazine on Chinese patients with treatment-refractory schizophrenia.

Clozapine has been shown to have superior effectiveness compared with classic neuroleptics in treating refractory schizophrenia in Caucasians, but its efficacy and safety in Chinese have not been adequately studied. Forty Chinese schizophrenic patients were recruited in a 12-week, double-blind, comparative trial. Twenty-one patients were randomly assigned to clozapine treatment and 19 to chlorpromazine treatment. The average dose was 543 +/- 157 and 1163 +/- 228 mg/day for clozapine and chlorpromazine, respectively. The results showed that six clozapine-treated patients (28.6%) had more than 20% improvement in Brief Psychiatric Rating Scale score and were classified as responders, whereas none of the chlorpromazine-treated patients was classified as a responder. The degree of improvement in positive symptoms, negative symptoms and Brief Psychiatric Rating Scale scores in the clozapine group was inversely correlated with the severity of negative symptoms at entry into the trial. Two clozapine-treated patients were withdrawn from the study, one because of leukopenia and nausea, and the other because of vomiting and hypotension. Chlorpromazine treatment was prematurely discontinued in two patients, because of jaundice and over sedation in one, and because of severe weight loss in the other (9 kg). The rate of moderate-to-severe sialorrhea was high in clozapine-treated patients (28.6%). Two clozapine-treated patients and two chlorpromazine-treated patients showed significant improvement in previously existing tardive dyskinesia and one chlorpromazine-treated patient exhibited aggravation of tardive dyskinesia. The results of this study indicate that clozapine treatment might have advantages over chlorpromazine for Chinese schizophrenic patients who are refractory to typical neuroleptic treatment.

Adult↗

Risk factors for Alzheimer's disease: a case-control study.

The extent of current knowledge of risk factors for Alzheimer's disease (AD) is still limited. We conducted a case-control study of 98 AD patients and 98 age- and sex-matched controls. Light smoking had a decreased risk for AD (AD: 2.0%, controls: 21.4%, odds ratio = 0.10, p = 0.003), whereas daily smoking showed a trend to increase the risk for AD (AD: 45.9%, controls: 26.5%, odds ratio = 1.73, p = 0.08). After multivariable analyses factors associated with AD included the presence of apolipoprotein epsilon4 allele, and the duration of well water consumption.

Aged↗

Epsilon 4 allele of apolipoprotein E increases risk of Alzheimer's disease in a Chinese population.

We examined the apolipoprotein E genotype in 56 Chinese patients with late-onset sporadic Alzheimer's disease (AD) and 57 Chinese control subjects of similar age. The frequency of epsilon 4 in the AD group was significantly higher than that in the control group (23.2% versus 7.9%, p = 0.003). The odds ratio for AD in individuals with either one or two epsilon 4 was 2.96 (95% CI 1.11 to 8.03). The linear trend for AD in proportion to alleles of epsilon 4 was also significant (chi 2 = 8.2, p = 0.004). Our results support the association between epsilon 4 and AD in the Chinese.

Age of Onset↗

Paroxetine in the treatment of Chinese patients with depressive episode: a double-blind randomized comparison with imipramine.

BACKGROUND: Paroxetine is a potent inhibitor of serotonin re-uptake. Although it has been widely used as an antidepressant in western countries, its efficacy and side effects in the Chinese are unknown. METHODS: Patients with major depressive episode were recruited from the outpatient clinic and the acute wards of the Department of Psychiatry, Veterans General Hospital-Taipei in 1994. Severity of depression was evaluated with Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression (CGI) and the adverse effects were evaluated with Treatment Emergent Symptom Scale (TESS). Forty Chinese patients with HAM-D scores > or = 18 at the beginning of the first dose were randomized to receive paroxetine (20 to 30 mg/day) or imipramine (100 to 125 mg/day). The dosage was designed as a fixed-adjustable regimen for an active treatment period of six weeks. The patients and the clinical investigators were both blind to the medication until the end of the trial. RESULTS: Five patients violating the trial protocol were excluded from this study, leaving 35 patients for efficacy and adverse effect analyses. Sixty-seven percent (12/18) of paroxetine-treated patients and 65% (11/17) of imipramine-treated patients showed a 50% or more reduction in HAM-D scores. The rate of patients whose mood recovered to normal or near-normal (borderline) was higher in the paroxetine group (66.7%) than in the imipramine group (35.3%), but the difference was not statistically significant (p = 0.13). At the end of this trial, the mean reduction of HAM-D scores was similar between groups (20.2 +/- 9.1 vs 15.3 +/- 8.4, p > 0.1). Three patients in the paroxetine group and two patients in the imipramine group withdrew prematurely due to adverse effects of impatience. Adverse effects of anticholinergic effects were reported more frequently in the imipramine group than in the paroxetine group (p = 0.01). CONCLUSIONS: In comparison with imipramine, paroxetine affords fewer anticholinergic adverse effects without the sacrifice of efficacy in the treatment of depressed Chinese patients.

Adult↗