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Jan-Gowth Chang

Publications and source records attributed to Jan-Gowth Chang.

At least 37 records · Page 2Linked to original sources
PubMed2004

DAT polymorphism and diverse clinical manifestations in methamphetamine abusers.

The clinical outcome for methamphetamine (MAP) abusers is variable. MAP exerts its biological activity through rapid conversion to amphetamine (AP) and MAP itself. The dopamine transporter (DAT) is the main modulator of MAP/AP-induced dopamine release and dopamine neurotoxicity, and is also the major regulator of dopamine level in the brain. We tested for an association between a DAT-gene polymorphism and clinical variations in MAP abusers. A total of 146 MAP abusers were enrolled in the study and classified into three clinically distinct groups: MAP dependence (n = 30), MAP psychosis (n = 88) and chronic MAP psychosis (n = 28). Patients with schizophrenia (n = 79) and healthy controls (n = 72) were also recruited for the study. The 40 base pair variable number tandem repeat polymorphism in the 3'-untranslated region of the DAT was the focus of the investigation. The subjects were all Chinese residents of Taiwan. The respective allelic frequencies for DAT repeats 11, 10 and 9 were 0.067, 0.833 and 0.083 for the MAP-dependence group, 0.006, 0.864 and 0.119 for the MAP psychosis group, 0.018, 0.893 and 0.089 for the chronic MAP psychosis group, 0.019, 0.911 and 0.07 for the schizophrenic controls, and 0.021, 0.889 and 0.083 for the healthy controls. No significant associations were demonstrated between this DAT polymorphism in genotype and allele frequency and the clinical outcome of MAP abusers. The biological relevance of the variable number tandem repeat polymorphism in the 3'-untranslated region of DAT in MAP abusers was not demonstrated in this study.

3' Untranslated Regions↗
PubMed2004

Promoter CpG methylation of tumor suppressor genes in colorectal cancer and its relationship to clinical features.

Aberrant promoter methylation of CpG islands of tumor suppressor genes inhibits expression of the genes and may lead to tumorigenesis. We investigated the aberrant methylation profile of potential tumor suppressor genes of p15, p16, SOCS-1, and Wnt signaling pathway in colorectal cancers and correlated the data with clinical findings. Cancerous and nearby non-cancerous tissues of 185 sporadic colorectal cancer samples were studied. Methylation specific PCR was performed to explore the mechanism of inactivation in p15, p16, SOCS-1, E-cadherin, APC, GSK-3beta, and Axin1 genes. Aberrant promoter methylation in p15, p16, SOCS-1, E-cadherin, APC, GSK-3beta, and Axin1 genes were 5.9, 7.0, 3.8, 5.9, 12.4, 2.2, and 0% for cancerous tissues, respectively, whereas the frequencies were 3.8, 0, 0, 7.0, 2.7, 0.5, and 0% for nearby non-cancerous tissues, respectively. The frequency of aberrant promoter methylation of cancerous tissues was significant higher than non-cancerous tissues in p16, SOCS-1, and APC genes (p<0.05) and methylation status of these genes had no clear relationship with clinical parameters. Of the 66 patients who showed at least one aberrant promoter methylation in the tumor-suppressor genes, 5 (7.6%) patients demonstrated multiple methylation phenotype (methylation > or =3) and associated with increased lymph node metastasis (p=0.036). Our findings suggest that inactivation of some tumor suppressor genes through aberrant promoter methylation of CpG islands may play a role in the development of colorectal cancer and methylation inactivation of these genes except p16 and SOCS1 may occur at the precancerous stage. Multiple methylation pathways may be involved in the tumorigenesis of colorectal cancer and associated with aggressiveness of clinical disease.

Base Sequence↗
PubMed2004

Mutational, epigenetic and expressional analyses of caveolin-1 gene in breast cancers.

Caveolin-1, an integral membrane protein of caveolae found in many cell types, has been suggested as a candidate tumor suppressor. However, the mechanism underlying caveolin-1 decreased expression is not fully understood. The purpose of this study is to investigate the role of aberrant promoter methylation in the regulation of caveolin-1 gene in breast cancer correlated with clinical findings. We used methylation specific PCR, direct sequencing and immunohistochemistry stain methods to explore the role of caveolin-1 gene in the development of breast cancer. We demonstrated that 14 of 55 cases (25.5%) and 4 of 55 cases (7.3%) had methylated CpG-island on caveolin-1 promoter in cancerous and non-cancerous cells, respectively. The frequency of aberrant promoter methylation of breast cancer tissues was significant higher than non-cancerous tissues (p<0.05). There were four types of methylation pattern of caveolin-1 gene in the breast cancer tissues. No mutation but one polymorphism GAC right curved arrow GAT at codon 82 was found in the whole exonic sequences of caveolin-1 gene. The methylation status of caveolin-1 gene had no clear relationship with age, cell grade, stage of tumor, and status of estrogen receptor, p53 and c-erbB2 in the breast cancer tissues. However, in breast tissue with aberrant promoter methylation of caveolin-1 gene, the presence of progesterone receptor showed borderline statistic difference compared to unmethylated promoter (p=0.11). Immunohistochemistry demonstrated that expression of caveolin-1 gene correlated with aberrant promoter methylation status in sporadic breast cancer tissues. Our findings suggest that aberrant promoter methylation of caveolin-1 gene is associated with inactivation of expression. This process occurs in the precancerous stage and may play an important role in the development of breast cancer.

Base Sequence↗
PubMed2004

Glutathione S-transferase T1 deletion is a risk factor for developing end-stage renal disease in diabetic patients.

Reactive oxygen metabolites may contribute to the development of end-stage renal disease (ESRD) in diabetic and hypertensive patients. In this study, we used multiplex polymerase chain reaction (PCR) to analyze polymorphisms of two endogenous antioxidant genes, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), and to determine their role in the development of ESRD in diabetic and hypertensive patients. Our results showed that homozygous deletion of the GSTT1 gene is a risk factor for developing ESRD in diabetic patients (p=0.004, OR=2.18, 95% confidence interval (CI) =1.29-3.70), but not in hypertensive patients. No association between homozygous deletion of GSTM1 and the development of ESRD was found in either diabetic patients or hypertensive patients. These results indicate that genetic variations in enzymes involved in free radical metabolism are associated with the development of ESRD in diabetes mellitus (DM) patients, and may permit the targeting of preventive and early intervention strategies to high-risk individuals.

Diabetes Mellitus, Type 1↗
PubMed2003

Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer.

Glycine N-methyltransferase (GNMT), a multifunctional protein involved in the maintenance of the genetic stability, is often down-regulated in hepatocellular carcinoma (HCC). Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer. Six novel polymorphisms, including two short tandem repeats, one 4-nucleotide insertion/deletion polymorphism, and three single nucleotide polymorphisms, in GNMT were identified in this study. The rates of loss of heterozygosity at the GNMT locus in pairs of normal and tumor tissue from the HCC patients were approximately 36-47%. In addition, the observed heterozygosity of GNMT decreases in tumor adjacent liver DNA from HCC patients compared with that observed in blood DNA from normal individuals and HCC patients. This may result from the early event of loss of heterozygosity within the GNMT gene in the liver tissues of HCC patients. However, in this study, we did not observe the association of polymorphic GNMT alleles as inherited risk factors for HCC. We also elucidated the functional impact of genetic markers in the GNMT promoter by performing luciferase reporter gene and gel mobility shift assays. The results indicate that two polymorphisms, short tandem repeat 1 and insertion/deletion polymorphism, in the promoter region could cause allelic specific effects on the transcriptional activity of GNMT. The risk genotypes of GNMT, which presumably have a lower expression level, as estimated from in vitro functional studies, are over-represented in tumor-adjacent tissues from HCC patients. In summary, our results suggest that GNMT alteration may be an early event in HCC development and that GNMT could be a new tumor susceptibility gene for HCC.

Alleles↗
PubMed2003

The association of beta-site APP cleaving enzyme (BACE) C786G polymorphism with Alzheimer's disease.

The deposition of amyloid beta-peptide (Abeta) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Beta-site APP cleaving enzyme (BACE) is the rate-limiting enzyme in the Abeta formation. BACE mutations/polymorphisms may be associated with AD. We searched the BACE coding region mutations/polymorphisms of cDNA in 25 AD patients and 100 healthy controls by single-strand conformational polymorphism. A polymorphism at BACE coding region was identified and confirmed to be 786C/G polymorphism by nucleotide sequencing. Based on these findings, we investigated the association of this polymorphism with the occurrence of AD by PCR-RFLP. A total of 98 AD patients along with 138 controls were recruited in the present study. The allele frequencies of the 786C/G polymorphism were 0.622 for C and 0.378 for G in AD. In controls, the C and G allele frequencies were 0.691 and 0.309, respectively. No significant association of this polymorphism with the occurrence of AD can be established. Larger sample size may be necessary to identify other potential mutations/polymorphisms among BACE gene.

Aged↗
PubMed2003

CYP3A5*1 is an inhibitory factor for lung cancer in Taiwanese.

The expression of the cytochrome P450 CYP3A5 enzymes shows a wide variation across the general population and ethnic groups. This wide disparity implies interracial differences in drug clearance and susceptibility to diseases such as cancer. CYP3A5 polymorphisms were rapidly determined using polymerase chain reaction-restriction fragment length polymorphism analysis in 113 Taiwanese patients with hepatoma, 70 with cervical cancer, 92 with breast cancer, 82 with oral cancer, 90 with thyroid cancer, 133 with lung cancer, and 270 healthy controls. The allelic frequencies of CYP3A5*1 were 25% in hepatoma patients, 33% in cervical cancer patients, 31% in breast cancer patients, 22% in oral cancer patients, 23% in thyroid cancer patients, 20% in lung cancer patients, and 27% in healthy subjects. Lung cancer patients had a significantly lower frequency (20%) of CYP3A5*1 expression than healthy controls (p = 0.028, odds ratio = 1.49, 95% confidence interval = 1.04-2.13), but there was no statistically significant difference between healthy controls and other cancers. We suggest that CYP3A5*1 may play an important role in individual predisposition to lung cancer in Taiwan.

Alleles↗
PubMed2003

Assocation of endostatin D104N with leukemia.

The bone marrow and/or peripheral blood from 126 patients with acute myeloid leukemia (AML), 57 with chronic myeloid leukemia (CML), 91 with acute lymphocytic leukemia (ALL), and 178 normal controls were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay to evaluate the association of the endostatin polymorphisms D104N (nucleotide 4349G --> A) with leukemia. In the 178 normal Taiwanese, the allele frequency of 4349G was 98% (348/356) and that of 4349A was 2% (8/356). The frequencies of homozygous 4349G (104D/D) and heterozygous 4349G/A (104D/N) were 95. 5% (170/178) and 4.5% (8/178), respectively. However, no individuals were homozygous 4349A (104N/N). Among the leukemia patients, 124/126 with AML (98.4%), 55/57 with CML (94.9%), and 89/91 with ALL (97.9%) were homozygous 4349G. In addition, 2/126 with AML (1.6%), 2/57 with CML (5.1%), and 2/91 with ALL (2.1%) were heterozygous 4349G/A. No patients were homozygous 4349A. Similar frequencies of endostatin polymorphisms were observed in leukemic patients and normal controls. This suggests that the endostatin polymorphism is not associated with the risk of leukemia.

Collagen↗
PubMed2003

Epigenetic alteration of the SOCS1 gene in chronic myeloid leukaemia.

The expression of the suppressor of cytokine signalling-1 (SOCS1) protein is induced in response to stimulation by several cytokines. The induced SOCS1 inhibits the signalling pathway through the association with a variety of tyrosine kinase proteins. In this study, the mutation analyses, CpG island methylation status, and the expression of the SOCS1 gene in 112 chronic myeloid leukaemia (CML) samples, five leukaemia cell lines, and 30 normal controls were analysed. No genetic mutations of SOCS1 gene were noted in the CML samples. The SOCS1 gene was hypermethylated in 67% and 46% of the blastic and chronic phase CML samples respectively (P < 0.0001). However, there was no methylation of the SOCS1 gene in normal controls or CML in molecular remission. The methylation status of the SOCS1 gene is consistent with the results of the real-time quantitative reverse transcription polymerase chain reaction and immunocytochemistry staining. Our results demonstrate that the SOCS1 gene silencing is caused by the methylation of CpG islands in CML and is reversed to an unmethylated status in molecular remission. As SOCS1 has universal activity to negatively regulate several cytokine signalling pathways, the loss of the negative regulation of cytokine signalling by the SOCS1 may play a role in the pathogenesis of CML progression.

Carrier Proteins↗
PubMed2003

The relationship among the polymorphisms of SULT1A1, 1A2 and different types of cancers in Taiwanese.

Sulfotransferase (SULT) enzymes play an important role in the detoxification, metabolism and bioactivation of numerous xenobiotics, many dietary and environmental mutagens, drugs, neurotransmitters and hormones. The genes for SULT1A1 and SULT1A2 contain common genetic polymorphisms that are associated with individual variations in the level of enzyme activities as well as variations of biochemical and physical properties. We developed a PCR-RFLP method to analyze the frequencies of SULT1A1 and SULT1A2 alleles among cancerous patients and normal controls in Taiwan. The results showed that SULT1A1*1 and SULT1A2*1 were in positive linkage disequilibrium. Neither SULT1A1*3 nor SULT1A2*3 were found in this study. The frequencies of SULT1A1*2 and SULT1A2*2 for hepatic, colon, lung, oral, gastric, renal and cervical cancerous patients were 3.95, 5.56, 4.92, 3.84, 2.70, 7.41 and 4.50%, respectively. No statistical significance was found for these cancer patients after comparison with normal controls (4.0%) for the allelic frequencies of SULT1A1*2 and SULT1A2*2.

Arylsulfotransferase↗
PubMed2003

Molecular basis for the RhD negative phenotype in Chinese.

RhD negative individuals are rare and only account for 0.3-0.5% of Taiwanese population. There are some variations among Chinese RhD negative individuals and the molecular basis of these variants is unknown. Two hundred and four RhD negative DNA samples were investigated by a modified polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and RT-PCR. Several representative cases were further studied using Southern blot analysis. Three types of genetic change in RhD negative individuals were discovered in the Taiwanese population. The most common one, accounting for 150 (73.5%) of 204 cases, was a deletion of the D gene with expression of normal ce or cE antigens (72.5% ce, and 1.0% cE), which were produced by the ce or cE allele of the RHCE gene. The second one, Del, was a deletion of 1013 bp between introns 8 and 9 including exon 9 of the RHD gene. This type accounted for 41 (20.1%) of 204 D negative individuals. The third type was caused by genomic rearrangement around intron 2 and intron 9 between the RHD and RHCE genes and it results in a hybrid gene (D-CE-D) with exons 1, 2 and 10 belonging to the RHD gene. This type of recombination accounted for 13 (6.4%) of 204 D negative individuals. The RhD negative variants found in this study are combination of two of the three alleles, described above. The PCR methods, which detect the differences in introns 1, 2 and 4 or exon 7 for differentiating D positive and D negative, are not reliable methods for studies in the Chinese population.

China↗
PubMed2003

Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers.

Caveolin-1 (CAV-1) protein, an integral membrane protein of caveolae membranes, is highly expressed in terminally differentiated cells and down-regulated in cells transformed by human papilloma virus infection. It may also be involved in the tumorigenesis of cervical cancer. CAV-1 gene is regarded as a candidate for the tumor suppressor gene and it can be inactivated in several ways, including point mutations, chromosomal deletions and promoter methylation. We used direct sequencing, methylation specific PCR, and immunohistochemical staining methods to explore the role of CAV-1 gene in the development of cervical cancer. Our results showed that 4 of 72 cases (6%) had methylated CpG-island on the CAV-1 promoter, 17 of 72 cases (26.1%) having no methylation on the promoter showed no expression of CAV-1 protein, and 2 of 72 cases had a GAC right curved arrow GAT transition polymorphism at codon 82. Three types of CAV-1 expression patterns were observed in cervical cancer tissues, and the expression pattern had no relationship with mutation status. From these results, we suggest that CAV-1 gene can be inactivated through mutations, and does not play a role, through methylation of promoter, or an unknown mechanism which may play a role, in the development of cervical cancer.

Adenocarcinoma↗
PubMed2003

Correlation between protein expression and epigenetic and mutation changes of Wnt pathway-related genes in oral cancer.

The components of the Wnt-signaling pathway are reported to be mutated in human cancer cells, but the relationship between the components and oral squamous carcinoma (SCC) is still unknown. In this study, we analyzed the epigenetic changes and expression patterns of four member proteins of the Wnt-signaling pathway and analyzed the mutations of beta-catenin and AXIN 1 genes, in order to explore the roles of the pathway in the development of oral cancer. The results showed that there are no beta-catenin and AXIN 1 gene mutations and no methylation of the CpG island of beta-catenin, AXIN I and GSK3beta genes in oral cancer cells; methylation of the CpG island of APC occurs in the precancerous stage and it is a dynamic change; the aberrant expressions or abnormal localization of the Wnt-signaling pathway proteins have no relationship with methylation status or mutation. From our results, we suggest that the Wnt pathway related genes play a very limited role in the development of oral SCC.

Adult↗
PubMed2002

JunB gene expression is inactivated by methylation in chronic myeloid leukemia.

JunB is a component of the Jun family genes of the activating protein-1 transcription factors that are important in the control of cell growth and differentiation and neoplastic transformation. Recently, it was demonstrated that transgenic mice specifically lacking JunB expression in the myeloid lineage developed a myeloproliferative disease, eventually progressing to blast crisis that resembled human chronic myeloid leukemia (CML). To gain further insights into the role of JunB in human CML, we examined peripheral blood from 17 healthy individuals and CML patients (11 in blastic crisis and 21 in chronic phase) by real-time quantitative reverse transcription-polymerase chain reaction analysis for the expression of JunB. The results showed the expression levels of JunB were significantly impaired in CML cases (blastic crisis < chronic phase < normal). Mutational analysis of the whole gene and methylation analysis of cytosine-phosphate guanosine (CpG) sites at the promoter area were further performed to investigate the possible mechanisms. However, no mutation was found within the coding region or the 9 flanking evolutionarily conserved regions in all CML cases. Interestingly, in the promoter area of JunB gene, most of the CpG sites were methylated in CML cases; in contrast, none of these CpG sites were methylated in normal cases. Demethylation by treatment of hypermethylated K562 cells with 5-aza-2'-deoxycytidine resulted in partial reactivation of JunB expression. Our results suggest that the down-regulated JunB expression in CML was due to the inactivation of JunB gene by methylation and the differential expression was correlated to the ratio of cells being methylated.

Azacitidine↗
PubMed2002

Molecular analysis of mutations and polymorphisms of the Lewis secretor type alpha(1,2)-fucosyltransferase gene reveals that Taiwan aborigines are of Austronesian derivation.

The origins of the Taiwan aborigines have not been fully resolved. Anthropological and linguistic studies have indicated that their ancestry is mainly Austronesian or Malayopolynesian. Some polymorphisms and mutations in the secretor type alpha(1,2)-fucosyltransferase (FUT2) gene are found in Taiwan aborigines. In this study, we analyzed the frequency of eight mutations and one polymorphism of the FUT2 gene in Taiwan aborigines and other ethnic groups in order to explore the origins of these groups. The results showed that the C302T, G428A, and fusion gene mutations were specific for Thai, Caucasians, and Japanese, respectively. The A385T mutation was specific for Asians including Taiwan aborigines. The genetic frequencies of C571T were much higher in Taiwan aborigines (1.96% to 20.4%), Filipinos (13.2%), and Indonesians (3.30%) as compared with Thai (0.57%), Chinese (0.65% to 1.12%), Japanese (0%), and Caucasians (0%). The frequencies of the G849A mutation were also higher in Taiwan aborigines (0.38% to 21.57%), Filipinos (6.80%), and Indonesians (1.48%) than in Thai (0.94%), Chinese (0-0.37%), Japanese (0%), or Caucasians (0%). Deletion of a 3-bp region (nt 688 to nt 690) was found only in Filipinos (0.85%), Indonesians (0.74%), and three tribes (0.42% to 2.70%) of Taiwan aborigines, but not in other populations. The C628T mutation was found only in Taiwanese Han, Thai, and two tribes of Taiwan aborigines. The genetic frequency of the C357T polymorphism was much higher in Asians than in Caucasians. The genetic analysis confirms that the origins of Taiwan aborigines are Austronesian and that they are closely related to the Filipino and Indonesian populations. We suggest that mutations or polymorphisms of the FUT2 gene are very good markers for investigating population genetics.

Australia↗