Biomedical subjects

C J Hong

Publications and source records attributed to C J Hong.

At least 19 recordsLinked to original sources

PubMed2005

Cholinesterase inhibitor affects the amyloid precursor protein isoforms in patients with Alzheimer's disease.

An altered platelet ratio of amyloid precursor protein (APP) isoforms might be a diagnostic, predictive, or therapeutic marker for Alzheimer's disease (AD). Our purpose was to test the hypothesis that this ratio might serve as a therapeutic marker for AD patients treated with the cholinesterase inhibitor, galantamine. Thirty-nine patients (mean age 76.6 +/- 9.4 years) with AD were treated with galantamine for 12 weeks. Patients were evaluated at baseline, 4 and 12 weeks by cognitive testing along with a determination of their platelet APP isoform ratio. Western blotting was performed to calculate the APP isoform ratio. At the end of the treatment, cognitive scores significantly improved, and the ratio of the high-molecular-weight (130 kDa) isoform to the low-molecular-weight (110-106 kDa) isoforms increased. These results suggest that cholinesterase inhibition might be involved in APP processing.

Aged↗

PubMed2004

Estrogen-metabolizing gene COMT polymorphism synergistic APOE epsilon4 allele increases the risk of Alzheimer disease.

Alzheimer disease (AD) is a polygenic multifactorial disorder. Several studies suggested that the neuroprotective effect of estrogen was based on an APOE-dependent mechanism. The goals of the current study were to determine if the genes involved in estrogen metabolism were linked to the risk of AD and find out if there was an interaction between estrogen-metabolizing gene polymorphisms and the APOE epsilon4 allele in the risk of prevalent AD. We investigated 66 patients with AD and 86 age- and gender-matched normal subjects. The polymorphisms of APOE and estrogen-metabolizing genes CYP17, CYP1A1 and COMT were examined. No association was found between each estrogen-metabolizing gene polymorphism and AD. However, the COMT HH genotype and APOE epsilon4 allele had a synergistic effect on the risk of AD. Taking subjects with epsilon4-epsilon4-/HH- as reference, the risk of developing AD in subjects with one epsilon4 allele (epsilon4+epsilon4-/HH-) was 2.6 (95% confidence interval, CI, 0.7- 9.1); however, the risk in subjects with both HH and one epsilon4 (epsilon4+epsilon4-/HH+) increased to 3.6 (95% CI 1.2-10.6). The subjects with homozygous epsilon4 still had the highest risk in developing AD (odds ratio 6.6, 95% CI 0.6-69.6). The p value of the linear trend test for this regression model was 0.004. It is possible that a high metabolism of estrogen by COMT may have reduced the protective effect of estrogen in AD. Further studies to clarify this interaction may improve our understanding of the generic risks for AD.

Aged↗

PubMed2004

ApoE epsilon4 allele is associated with incidental hallucinations and delusions in patients with AD.

Of 135 patients with Alzheimer disease (AD), 56 without psychiatric symptoms at the first visit were followed for a mean period of 51.9 +/- 10.3 months to identify incident psychiatric symptoms. The hazard ratios of ApoE epsilon4 allele in developing psychiatric symptoms were calculated by Cox regression hazard analyses. The presence of the ApoE epsilon4 allele carried a 19.0-fold risk for developing hallucinations and a 3.4-fold risk for delusions.

Aged↗

PubMed2003

Association study of the dopamine and serotonin transporter genetic polymorphisms and methamphetamine abuse in Chinese males.

The dopamine transporter (DAT) and the serotonin transporter (5-HTT) play important roles in methamphetamine (METH) dependence because they are the target of METH action. For this study, the association between the DAT and 5-HTT polymorphisms and METH dependence were investigated for a Chinese-male sample population. The investigated polymorphisms included those of the DAT 3'-variable number tandem repeat, the 5-HTT gene promoter and a 5-HTT variable number tandem repeat polymorphisms. No significant difference was demonstrated for genotype or allele frequency, when comparing METH dependent and control cases for the DAT and the 5-HTT polymorphisms. The findings of this study suggest that these polymorphisms do not play major roles in METH dependence in the Chinese-male population.

Adult↗

PubMed2001

Association study of the p53-gene Pro72Arg polymorphism in schizophrenia.

The p53 tumor-suppressor gene, encoding a phosphoprotein, is a key element in maintaining genomic stability and cell apoptosis. It is also implicated in nervous-system development. In order to examine the role of the p53 gene for the pathogenesis of schizophrenic disorders, patients (n=155) and control subjects (n=168) were genotyped for the p53-Pro72Arg polymorphism. The results demonstrated no association with schizophrenia and/or age of onset for this polymorphism.

Adult↗

PubMed2001

Association between tryptophan hydroxylase gene polymorphism (A218C) and schizophrenic disorders.

The human tryptophan hydroxylase (TPH) gene, the rate-limiting enzyme in serotonin biosynthesis, was localized on human chromosome 11p14-p15.3. Variation within intron 7 of the TPH gene was found to influence serotonin metabolism in the brain. To explore the possible role of TPH in the pathogenesis of schizophrenic disorders, we genotyped the TPH A218C polymorphism in 196 schizophrenic patients and 251 controls. The results demonstrated that genotype distribution was significantly different between schizophrenic patients and control subjects (P=0.002). No association was found between TPH genotypes and suicidal history in schizophrenic patients (P=0.239). The positive finding in this study suggests that the TPH 218A allele is a risk factor for schizophrenic disorders or is in linkage disequilibrium with the putative schizophrenia susceptibility locus in Han Chinese population.

Acute Disease↗

PubMed2001

Association analysis of polymorphism in the promoter region of the alpha2a-adrenoceptor gene with schizophrenia and clozapine response.

There exists considerable evidence implicating the alpha (alpha) adrenergic system in the superior therapeutic effects of clozapine for the treatment of schizophrenia, as also its associated adverse hypersalivation side effect. It would seem plausible for variants of the adrenoceptors to be associated with the clozapine response. The present study tested the hypothesis that a biallelic polymorphism in the promoter region of the alpha2a-adrenoceptor gene confers susceptibility to schizophrenia, and is associated with a clozapine-induced (favorable) therapeutic response and/or a clozapine-induced hypersalivation. Ninety-seven treatment-resistant schizophrenic patients were assessed using the Brief Psychiatric Rating Scale before and after clozapine treatment. The results of clozapine treatment demonstrated that the alpha2a-adrenoceptor gene variants did not play a major role in the susceptibility, hypersalivation adverse effect or clozapine response of patients with schizophrenia. The polymorphism of the alpha2a-adrenoceptor gene investigated is not likely to play a major role in the pathogenesis of schizophrenic disorders or clozapine response, although the hypothesis that these genes are implicated in the cognitive deficit and polydipsia associated with schizophrenic disorders may, however, still warrant further study.

Adult↗

PubMed2001

Association study between cannabinoid receptor gene (CNR1) and pathogenesis and psychotic symptoms of mood disorders.

Cannabis can induce mood change and sometimes psychotic symptoms in normal persons. In brain, the main active ingredient of cannabis acts via the cannabinoid CB1 receptor (CNR1) which is located on chromosome 6q14-15. Linkage studies have suggested the presence of a bipolar disorder susceptibility locus on chromosome 6q. In this population based association study, we tested the hypothesis that a microsatellite polymorphism in the promoter region of the CNR1 gene confers susceptibility to mood disorders and psychotic features. We genotyped the CNR1 gene is 154 mood disorder patients and 165 normal controls. The results showed that the triplet repeat polymorphism in the promoter region of the CNR1 gene was not likely to be involved in the pathogenesis or in the psychotic symptoms of mood disorders.

Adult↗

PubMed2001

Allelic variants of the alpha1a adrenoceptor and the promoter region of the alpha2a adrenoceptor and temperament factors.

Human personality traits are partially determined by genes. It has been suggested that the reward-dependence dimension assessed by the Tridimensional Personality Questionnaire (TPQ) is related to the central noradrenergic system. Our population-based association study tested the hypothesis that genetic variants of the adrenoceptor are associated with this personality trait. The alpha1a- and the alpha2a-adrenoceptor genotypes were determined for 198 healthy Han Chinese who had completed the TPQ. We found no significant differences for TPQ personality-factor scores, including reward dependence and its subscales, for subjects showing different adrenoceptor genotypes. Our negative findings suggest that polymorphisms of the alpha1a adrenoceptor and of the promoter region of the alpha2a-adrenoceptor have no major effect on the reward-dependence personality trait as assessed by TPQ.

Adult↗

PubMed2001

A study of alpha-adrenoceptor gene polymorphisms and Alzheimer disease.

There exists considerable evidence implicating abnormalities of the alpha (alpha)-adrenergic system in the development of Alzheimer disease (AD). We propose to investigate potential correlations between the presence or otherwise of alpha-adrenoceptor polymorphisms and the presence of AD. We studied the polymorphisms of the alpha1a- and the alpha2a-adrenoceptor genes in 142 AD patients and 98 normal controls. The result demonstrated that none of the alpha2a-adrenoceptor genotypes was associated with increased susceptibility to AD. However, there was a trend that the frequency of the C allele of the alpha1a-adrenoceptor was elevated and an excess of the CC genotype (90.1%) was found in the subjects with AD in comparison with the controls (78.6%). This association was unrelated to the apolipoprotein E genotypes. The hypothesis that the alpha1a-adrenoceptor gene may be implicated in the pathogenesis of AD may deserve further study.

Aged↗

PubMed2001

Association study of nicotinic-receptor variants and major depressive disorder.

BACKGROUND: Depressive patients are more likely to smoke than the general population and nicotine was found to reduce the incidence and severity of depressive symptoms in many studies. These findings suggest that nicotinic acetylcholine receptors (nAChRs) may be implicated in major depressive disorder. We tested the hypothesis that the allelic variant, 2 bp deletion, of the partially duplicated alpha7 nAChR gene confers susceptibility to major depressive disorder. METHODS: We genotyped alpha7 nAChR in 72 patients with major depressive disorder and 103 normal controls. RESULTS: The distribution of the partially duplicated alpha7 nAChR genotypes (P=0.027) and alleles (P=0.037) suggests a modest difference between depressive patients and controls. LIMITATIONS: The -2 bp allele is thought to be present only in the duplicated exon 6, and the impact of the partially duplicated alpha7 nAChR and its -2 bp variant remain to be determined. CONCLUSIONS: The -2 bp allele of partially duplicated alpha7 nAChR may have an influence on the risk for development of major depressive disorder. The levels of significance achieved are modest and the findings must be replicated in other studies.

Adult↗

PubMed2001

A study of apolipoproteins E and A-I in cutaneous amyloids.

BACKGROUND: Apolipoprotein E (apoE) is present in a variety of biochemically different amyloid deposits, including Alzheimer's disease, systemic amyloidosis and primary cutaneous amyloidosis (PCA). Among the three closely related alleleic forms of apoE, the epsilon4 allele is linked to Alzheimer's disease. Apolipoprotein A-I (apoA-I), another apolipoprotein, is also found in senile plaques of Alzheimer's disease and in amyloid of aortic atherosclerotic plaques. Furthermore, apoA-I has recently been found to be associated with hereditary cutaneous and cardiac amyloidosis. OBJECTIVES: To determine whether the apoE epsilon4 allele is associated with increased risk of PCA and whether apoE and apoA-I are present in PCA and common secondary cutaneous amyloidosis (SCA) (i.e. basal cell carcinoma, Bowen's disease and seborrhoeic keratosis). METHODS: We examined the apoE genotype in 57 Chinese patients with PCA and 58 normal healthy control subjects of similar age. In addition, immunohistochemical staining was performed to determine the localization of apoE and apoA-I in skin tissues from 15 patients with SCA and 15 with PCA. RESULTS: The frequency of the epsilon4 allele in the PCA group was not significantly higher than that in the control group (8.8% vs. 6.9%, P > 0.05). ApoE was present in amyloid deposits in both PCA and SCA, but apoA-I was not detected in these cutaneous amyloid deposits. CONCLUSIONS: ApoE is also a component of amyloid deposits in SCA. Although the genetic susceptibility of certain apoE isoforms may not be a crucial factor in the development of PCA and, although apoA-I is not associated with amyloid deposits of PCA and SCA, the role of apolipoproteins in amyloidogenesis deserves further scrutiny.

Adult↗

PubMed2001

Study of anticipation in Chinese families with schizophrenia.

The anticipation phenomenon is an important aspect in several genetic disorders in which the age at onset (AAO) decreases and the severity of illness increases in successive generations. This phenomenon has been reported in several schizophrenic family studies, and expanded repeat mutations are implicated. In the present study, we investigate the anticipation phenomenon in Chinese schizophrenic families. We compare the AAO between two generations of 38 unilinear schizophrenic families. Intergenerational comparisons show that the AAO was significantly earlier in the offspring generation (mean AAO, 22.2 years) than that in the parental generation (mean AAO, 31.0 years) (P < 0.001). When only including the offspring generation who married, the AAO difference between the two generations was not significant (28.4 years vs 31.0 years, P = 0.151). Our findings suggest that a selection bias in the parental group might greatly impact the study of anticipation in schizophrenia. Other unavoidable biases associated with these analyses are discussed in the text.

Adolescent↗

PubMed2001

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

A significant increase of 267C allele of the 5-HT(6) receptor gene has been reported in patients with Alzheimer's disease (AD). Because a deficit in serotonergic neurotransmission is involved in major depression, we tried to find out whether 267C allele is associated with depressive disorders in AD. A psychiatrist interviewed all AD patients and their caregivers for evidence of depression using a Chinese version of the Standard Clinical Interview for DSM-III-R. The difference in the 5-HT(6) genotype or allele distributions between the AD patients with depressive disorders (n = 25) and those without (n = 120) was not significant.

Aged↗

PubMed2001

Genetic variants of the serotonin system and weight change during clozapine treatment.

Clozapine-induced weight gain may impair health and affect patient compliance. The aim of this study is to investigate the relationship between the genetic variants of the serotonin system and clozapine-induced body weight change (BWC). Ninety-three treatment-resistant schizophrenic patients were weighed monthly for 4 months during clozapine treatment. At the conclusion of treatment, patients had gained an average of 2.4 kg body weight, with BWC ranging from -17.5 to +12.9 kg. The levels of the serotonin transporter variants, serotonin 2A, serotonin 2C and serotonin 6, demonstrated no statistically significant relationship to BWC. Patients with a lower initial body mass index demonstrated a greater weight gain associated with clozapine treatment. Further exploration of the neurotransmitters implicated in the antipsychotic-induced BWC is important in order to reduce the morbidity and noncompliance associated with weight gain.

Adolescent↗

PubMed2001

Estrogen receptor alpha gene polymorphism in schizophrenia: frequency, age at onset, symptomatology and prognosis.

Schizophrenic disorders are equally distributed for both sexes; however, later onset, milder psychopathology and better outcome are associated with the female gender. This sex difference is thought to be partly due to the estrogen system. Recent studies have determined that estrogen receptor alpha subtype (ER alpha) genetic polymorphisms may affect the expression of ER alpha, and are associated with Alzheimer's disease. For this study, we investigated the association of ER alpha polymorphisms for 125 schizophrenic patients and 142 control subjects. No significant differences for genotype distribution or allele frequency were revealed comparing controls and schizophrenic patients. The ER alpha genotypes were not associated with onset age, psychiatric symptoms or outcome for schizophrenic cases. With new research highlighting the prominent role of sex hormones in neurological and psychological dysfunction, further study is needed to explore the genetic effect of the sex hormone receptor gene on susceptibility mental disorders and associations with different phenotypes.

Adult↗

PubMed2001

Association analysis for dopamine D2 receptor Taq1 polymorphism with P300 event-related potential for normal young females.

P300 has been demonstrated abnormal for a variety of neuropsychiatric disorders, and heritability has been proposed. We analyzed the event-related potentials for three DRD2 genotype groups in 134 normal young females. The results demonstrate that there is no association for DRD2 genotype and P300 components. Our negative findings in normal subjects suggest association demonstrated for P300 latency and the DRD2 allele may be disease dependent.

Adult↗

PubMed2001

Association analysis for NMDA receptor subunit 2B (GRIN2B) genetic variants and psychopathology and clozapine response in schizophrenia.

It is known that a syndrome resembling schizophrenia is produced by the N-methyl-d-aspartate receptor antagonists. It has also been demonstrated that the level of an ionotropic N-methyl-d-aspartate 2B subunit (GRIN2B) of the glutamate receptor tends to increase after subchronic administration of clozapine, suggesting that GRIN2B may play an active role in the pathogenesis of schizophrenia and the function of clozapine medication. We studied 100 schizophrenic patients, investigating the associations for the GRIN2B genetic variants, and psychiatric symptoms and clozapine response. No significant differences were demonstrated comparing these three groups in terms of the baseline Brief Psychiatric Rating Scale (BPRS) score (P = 0.441). The percentage of patients scoring within 20% of baseline BPRS after clozapine treatment was similar for the three genotype groups (P = 0.132). A marginally higher mean clozapine dosage was revealed, however, for patients bearing the 2664C/C genotype (P = 0.013). Although replication of this research is required to confirm the results, an association for the GRIN2B C2664T polymorphism and clozapine treatment is suggested from our findings, which may assist in the prediction of optimal dosage for schizophrenic patients.

Adult↗