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Ying-Jay Liou

Publications and source records attributed to Ying-Jay Liou.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

Genetic analysis of the human ENTH (Epsin 4) gene and schizophrenia.

Numerous linkage studies suggest that chromosome 5q may be one of the important cytogenetic regions containing risk loci for schizophrenia susceptibility. Recently, genetic variations (rs254664 and rs10046055) in the intron 1 and 5' flanking regions of the ENTH (also known as Epsin 4) gene, which is located in 5q 33.3, have been demonstrated to be significantly associated with schizophrenia. The present study investigates whether this finding could be replicated in a population of Han Chinese, consisting of 269 patients with schizophrenia and 236 normal controls, by analyzing 9 single nucleotide polymorphisms (SNPs) ranging from the 5' upstream region to intron 8 of the ENTH gene and covering 96 kb. The results showed that we failed to identify the associations of rs1186922 and rs10046055 with schizophrenia. Although another genetic variation (rs1186922) showed a weak association with schizophrenia (uncorrected p value for alleles = 0.038), the significance did not survive after Bonferroni correction. This study thus fails to support an association of genetic variations in the ENTH gene and schizophrenia.

Adaptor Proteins, Vesicular Transport↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

Haplotype analysis of endothelial nitric oxide synthase (NOS3) genetic variants and tardive dyskinesia in patients with schizophrenia.

OBJECTIVES: Several studies have indicated the involvement of nitric oxide (NO) in the pathogenesis of tardive dyskinesia (TD), an incapacitating adverse movement disorder associated with long-term antipsychotic treatment. In human brain, the NO could be generated by endothelial nitric oxide synthase (NOS3). In this study, we studied whether the genetic variants in human NOS3 gene is associated with TD in patients with schizophrenia. METHODS: Two hundred and eighty-two chronic inpatients with schizophrenia treated with typical antipsychotics were recruited in this study. The patients were further grouped by the presence of TD or not according to the Research and Diagnostic Criteria for TD. The genetic variants in the NOS3 gene investigated in this study were -786T > C in the promotor region, 27-bp variable number of tandem repeats (27-bp VNTR) in intron 4, and Glu298Asp in exon 7. The frequencies of genotypes, alleles and haplotypes of the three markers were compared between the TD (n = 153) and non-TD (n = 129) groups. RESULTS: There were no significant associations between the genotypes and alleles of the three markers and TD. However, in the haplotype-based case-control analysis, the frequency of haplotype T-4b-Glu was significantly higher in non-TD than in TD group (TD vs. non-TD = 72.7% vs. 81.0%, permutation P value = 0.021, OR = 0.648, 95% CI = 0.432-0.973). CONCLUSIONS: We found that the haplotype T-4b-Glu represents a protective haplotype against TD after long-term antipsychotic treatment. This finding suggests that human NOS3 gene may be involved in the pathogenesis of TD.

Adult↗
PubMed2006

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↗
PubMed2005

No association between the ionotropic glutamate receptor kainate 3 gene ser310ala polymorphism and schizophrenia.

The etiology of schizophrenia has been suggested to be associated with the dysfunction of the glutamatergic system. A positive association between the ionotropic glutamate receptor kainate 3 gene (GRIK3) T928G polymorphism and schizophrenia has been reported, which suggests that people bearing G allele are at a higher risk for schizophrenia. Therefore, we attempted to replicate this study in Chinese with larger sample size. One hundred and sixty schizophrenic patients and 160 healthy controls participated in the current study. Genotype and allele distributions of GRIK3 T928G polymorphism in schizophrenics were similar to those of controls (p = 0.74 and p = 0.59, respectively). Our study indicated that there was no association between this polymorphism and schizophrenia, at least in Chinese.

Adult↗
PubMed2005

C825T polymorphism in the human G protein beta3 subunit gene is associated with long-term clozapine treatment-induced body weight change in the Chinese population.

Weight gain, leading to further morbidity and poor treatment compliance, is a common adverse effect of treatment with clozapine. The C825T polymorphism in the human G protein beta3 subunit gene has been noted to be associated with obesity, hypertension and coronary artery disease. Clozapine increases the level of G protein beta3 subunit in the rat striatum. The aim of the present study was to investigate the relationship between G protein beta3 polymorphisms and clozapine-induced body weight change in a Chinese population during long-term treatment. One hundred and thirty-four schizophrenic patients, who were treated with clozapine continuously (13.4+/-0.5 months), were genotyped for G protein beta3 subunit C825T polymorphism. None of these patients received second-generation antipsychotics before clozapine treatment. Body weight was monitored at baseline before clozapine treatment and at the endpoint after clozapine treatment. Patients with the TT type experienced significantly more weight gain (16.2+/-2.5%) compared to those with CT (9.3+/-1.2%) or CC types (5.5+/-2.4%) after long-term clozapine treatment (P = 0.003). Further stratification by gender demonstrated that the effect of C825T polymorphism on weight gain remained significant both in males and females. These findings confirm the importance of genetic factors in body weight change induced by long-term clozapine treatment in patients with schizophrenia, and indicate a role for the G protein beta3 subunit in body weight regulation during long-term clozapine treatment.

Adult↗
PubMed2004

Cytochrome P-450 2D6*10 C188T polymorphism is associated with antipsychotic-induced persistent tardive dyskinesia in Chinese schizophrenic patients.

Typical antipsychotic treatment had been postulated to be a risk factor for the susceptibility to tardive dyskinesia (TD). The cytochrome P-450 debrisoquine/sparteine hydroxylase (CYP2D6) metabolizes a majority of antipsychotics and exhibits various phenotypes on enzymatic activities from poor metabolizers to ultrarapid metabolizers. The various phenotypes are encoded by polymorphic genetic variants on the CYP2D6 gene. Although several studies had explored the association between the CYP2D6*10 C188T polymorphism, which encodes the phenotype intermediate metabolizers, and TD in Orientals, the findings were inconclusive. In the present study, we examined the relationship between the CYP2D6*10 C188T polymorphism and the TD occurrence in 216 Chinese schizophrenic patients (113 patients with TD and 103 patients without TD) and explored the correlation between the TD severity assessed by the Abnormal Involuntary Movement Scale (AIMS) and each C188T genotype in the 113 TD patients. Using logistic regression analysis, we found a modest association (p = 0.045) between TD and C188T genotypes. This positive finding was only observed in male patients (p = 0.001), but not in females. Our findings also support the correlation between AIMS scores and C188T polymorphism within the TD group after adjusting for confounding effects with the multiple regression analysis (p = 0.033). We concluded that the CYP2D6*10 C188T polymorphism may be associated with the susceptibility to the occurrence of TD induced by typical antipsychotics, especially in male patients, and may also be correlated with AIMS scores in TD patients.

Adult↗
PubMed2004

Association study of a functional catechol-O-methyltransferase genetic polymorphism with age of onset, cognitive function, symptomatology and prognosis in chronic schizophrenia.

The gene coding for catechol-O-methyltransferase (COMT), which is involved in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. This study aimed to assess the relationship between a functional polymorphism (Val158Met) of the COMT gene and age of onset (AOO), symptomatology, global cognitive function and prognosis in patients with schizophrenia. The study enrolled 154 patients with schizophrenia from chronic wards. Results failed to show a significant association between the Val158Met polymorphism and the Brief Psychiatric Rating Scale scores, Mini-Mental State Examination scores, and Social and Occupational Functioning Assessment Scale scores, but COMT Val158Met heterozygotes had a later AOO than homozygous patients. However, by further expanding the number of patients to 228 patients, the differences in AOO among the three COMT genotypic groups was not significant. The COMT Val158Met polymorphism did not appear to significantly affect susceptibility, symptomatology, global cognitive function and prognosis in Chinese patients with schizophrenia, but the possible association with AOO merits further investigation.

Adolescent↗
PubMed2004

Association analysis of the dopamine D3 receptor gene ser9gly and brain-derived neurotrophic factor gene val66met polymorphisms with antipsychotic-induced persistent tardive dyskinesia and clinical expression in Chinese schizophrenic patients.

The association between the dopamine D3 receptor (DRD3) ser9gly genetic polymorphism and tardive dyskinesia (TD), a serious adverse motor disorder after long-term antipsychotic treatment, has been studied extensively in recent years. However, the existence of inconsistent reports makes the role of the DRD3 ser9gly polymorphism in TD development questionable. In rodent studies, the DRD3 expression could be controlled by the brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family. In this study, we examined the association between the DRD3 ser9gly and BDNF val66met genetic polymorphisms and TD occurrence in 216 schizophrenic patients (TD/non-TD = 102/114). In addition, we also studied the effects of the DRD3 ser9gly and BDNF val66met genotypes and their gene-gene interaction on the clinical expression of TD in these TD patients. We found that the TD patients who were heterozygous for the BDNF genotypes had significantly higher abnormal involuntary movement scale (AIMS) orofacial scores (corrected p = 0.021, Bonferroni correction), and a trend of higher AIMS total and limb-trunk scores than the combined homozygous analogs. The correlation between the DRD3 ser9gly genotypes and its interaction with the BDNF val66met polymorphism, and the three classes of AIMS scores were not statistically significant. Furthermore, neither the DRD3 nor the BDNF genotypes and alleles were demonstrated to be associated with TD occurrence. We concluded that the BDNF val66met genetic polymorphism may exert its effect on the clinically phenotypic variability after TD has occurred. Further replication studies with larger sample size and stringent definition for TD is necessary.

Adolescent↗
PubMed2003

Association analysis for neuronal nitric oxide synthase gene polymorphism with major depression and fluoxetine response.

Nitric oxide (NO) is produced from its precursor L-arginine by the enzyme NO synthase (NOS), which includes at least three distinct isoforms - neuronal (nNOS), endothelial, and inducible NOS. Recent studies have implicated NOS in the mechanism that underlies the therapeutic efficacy of antidepressant medication. In addition, major depressive disorder (MDD) patients were found to have significantly higher plasma nitrate concentrations than normal subjects, an index of NO production, in comparison to normal subjects. In a population-based association study, we tested the hypothesis that the nNOS C276T polymorphism confers susceptibility to MDD. We also examined the association between this polymorphism and therapeutic fluoxetine response in 114 MDD patients who underwent a 4-week fluoxetine treatment. The results demonstrate that the nNOS variants are found at similar frequencies in MDD patients and healthy control subjects. Further, we did not discover any genetic variants that influenced the fluoxetine response in MDD patients treated with fluoxetine. Our findings suggest that this nNOS C276T polymorphism does not play a major role in the susceptibility to, or fluoxetine response in, MDD. However, the association between other NOS variants and MDD or antidepressant response, including sexual dysfunction, may warrant further investigation.

Adult↗
PubMed2003

Association analysis of the genetic variants of the N-methyl D-aspartate receptor subunit 2b (NR2b) and treatment-refractory schizophrenia in the Chinese.

Several pieces of evidence showed that N-methyl D-aspartate (NMDA)-receptor-mediated decreases in function may be a causative factor for schizophrenia. The NMDA receptors are composed of a common glutamate receptor, an ionotropic NMDA 1 (GRIN1) subunit and one of four GRIN2 subunits (GRIN2A-GRIN2D), combined in an undetermined ratio to make up the receptor complex. In this study, we tested the hypothesis of whether the GRIN2B 366C/G and 2664C/T genetic polymorphisms are related to Chinese treatment-refractory schizophrenic patients. 193 treatment-refractory schizophrenic patients and 176 normal subjects were recruited for this study. The results demonstrated that the genotype distribution was similar between schizophrenic patients and control subjects in 366C/G (p = 0.88) and 2664C/T (p = 0.336), but we found a higher mean clozapine dosage in 2664C/C genotype patients. These results show that GRIN2B genetic variations were not a major risk factor for treatment-refractory schizophrenic patients, but may influence the effect of clozapine during treatment.

Adult↗