Biomedical subjects

Dae-Yeon Cho

Publications and source records attributed to Dae-Yeon Cho.

9 recordsLinked to original sources

PubMed2006

Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population.

Panic disorder may be associated with defective serotonin (5-HT) neurotransmission. This study was to investigate the association between the tryptophan hydroxylase (TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with panic disorder in a Korean population. 244 Korean patients with panic disorder and the 227 controls were genotyped by a polymerase chain reaction-based method. The severity of panic disorders was assessed by number of panic attacks during the previous 1 month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). All the subjects completed the assessment measures including Spielberger State-Trait Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait (STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R), Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale--Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton Depression Rating Scale (HAMD). Responder analyses were conducted based on changes in CGI-I scores after 10 weeks of treatment. We found no significant differences in the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between the panic patients and the control group. Subgroup analyses in terms of comorbidities, response, and other primary clinical variables, indicated no differences in these polymorphisms. Our findings suggest that the TPH A218C polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and clinical symptomatologies, at least in a Korean population.

Age of Onset↗

PubMed2006

BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations.

We analyzed the mutation spectrum of BRCA1 and BRCA2 genes in 354 Korean breast cancer patients. Overall, 40 patients carried 25 distinct BRCA1/2 mutations including 12 novel mutations. Seven district mutations were found in multiple unrelated patients, with the BRCA2 c.7480C>T mutation detected in eight unrelated patients, accounting for 50% of the mutations detected in BRCA2. The large number (25/40, 62.5%) of recurrent mutations suggests the possibility of developing a simple screening test for these mutations. The frequency of mutations was related to the number and kinds of risk factors, varying from 10.4 to 25% in the five major risk factor groups. The frequency of BRCA mutations in patients with two or more risk factors was markedly higher than that in patients with one risk factor.

BRCA1 Protein↗

PubMed2005

Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk.

PURPOSE: Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity, which in turn may affect the risk of breast cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in breast cancer, we conducted a hospital-based case-control study of Korean women. EXPERIMENTAL DESIGN: We included 872 incident breast cancer cases and 671 controls recruited from several teaching hospitals in Seoul from 1995 to 2002. Twelve loci of selected DNA repair genes were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (XRCC2 Arg188His, XRCC4 921G > T, XRCC6 1796G > T, LIG4 1977T/C, RAD51 135G > C, 172G > T, RAD52 2259C > T, LIG1 551A > C, ERCC1 8092A > C, 354C > T, hMLH1 -93G > A, and Ile219Val). RESULTS: We found that the RAD52 2259 CT or TT, hMLH1 -93 GG, and ERCC1 8092 AA genotypes were associated with breast cancer risk after adjustment for known risk factors [odds ratio (OR), 1.33; 95% confidence interval (95% CI), 1.02-1.75; OR, 1.31; 95% CI, 0.99-1.74; and OR, 0.58; 95% CI, 0.38-0.89, respectively]. When Bonferroni's method was used to correct for multiple comparisons for nine polymorphisms with P = 0.005, all of these associations were not significant. However, the effects of RAD52 2259 CT or TT and ERCC1 354 CT or TT genotypes were more evident for the estrogen/progesterone receptor-negative cases (OR, 2.03; 95% CI, 1.24-3.34 and OR, 1.99; 95% CI, 1.35-2.94, respectively). CONCLUSION: Our findings suggest that genetic polymorphisms of RAD52, ERCC1, and hMLH1 may be associated with breast cancer risk in Korean women.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Array-based mutation detection of BRCA1 using direct probe/target hybridization.

We describe here an efficient microarray-based multiplex assay to detect Korean-specific mutations in breast cancer susceptibility gene BRCA1 using direct probe/target hybridization. Allele-specific oligonucleotides were covalently immobilized on an aldehyde-activated glass slide to prepare an oligonucleotide chip. From a wild-type sample, a two-step method was used to generate labeled multiplex polymerase chain reaction (PCR) amplification products of genomic regions containing the mutation sites. Amino allyl-dUTP, an amine-modified nucleotide, was incorporated during multiplex PCR amplifications and a monofunctional form of cyanine 3 dye was subsequently attached to the reactive amine group of the PCR products. Hybridization of the labeled PCR products to the oligonucleotide chip successfully identified all of the genotypes for the selected mutation sites. This work demonstrates that oligonucleotides chip-based analysis is a good candidate for efficient clinical testing for BRCA1 mutations when combined with the indirect strategy to prepare labeled target samples.

BRCA1 Protein↗

PubMed2005

The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine transporter density in Korean children with attention deficit hyperactivity disorder: relating to treatment response to methylphenidate.

The symptoms of attention deficit hyperactivity disorder (ADHD) can be treated with methylphenidate (MPH), a potent blocker of dopamine transporter (DAT). The homozygosity of the 10-repeat allele at the DAT gene (DAT1) seems to be associated with a poor response to MPH in children with ADHD. In the present study, we investigated the association between DAT density using I-123-N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane [123I]IPT single photon emission computed tomography (SPECT)] and the homozygosity for 10-repeat allele at DAT1 and response to MPH in Korean children with ADHD. Eleven drug-naive children with ADHD were included in the study and treated with MPH for about 8 weeks. After the genotyping and SPECT were performed, we compared DAT density between ADHD children with and without the homozygosity for 10-repeat allele at DAT1 and investigated the correlation between the homozygosity for 10-repeat allele and response to MPH. ADHD children with 10/10 genotype (n=7) had a significantly greater increase of the DAT density in basal ganglia than the children without 10/10 genotype (n=4). We found that while only 28.6% (2/7) of the subject with 10/10 genotype showed good response to MPH treatment, 100% (4/4) of the subjects without 10/10 genotype showed good response to MPH treatment. Our findings support an association between homozygosity for 10-repeat allele at DAT1 and the DAT density assessed in vivo and correlation between the homozygosity for 10-repeat allele and poor response to MPH.

Alleles↗

PubMed2004

The finding of new genetic polymorphism of UCP-1 A-1766G and its effects on body fat accumulation.

A-1766G polymorphism, for the first time, has been found in the sequencing of pooled and individual genomic DNA of Korean subjects at the 5' flanking region of the UCP-1 gene. The effects of new polymorphism on body fat were elucidated among 387 Korean female subjects. It was shown that the genotypes AA, AG, and GG were consisted of 57.4%, 37.7%, and 4.9%, respectively, which was in agreement with Hardy-Weinberg equilibrium (P=0.327). The frequency of major A allele was 0.762 and that of minor G allele was 0.238. It is found that the waist-hip ratio (WHR) (P=0.008), body fat mass (P=0.023), and percent body fat (P=0.014) are significantly higher in the AG/GG type compared to the AA type. When the subjects were analyzed using computerized tomography, there were significant increases in the AG/GG type compared to the AA type in the abdominal subcutaneous fat (P=0.015) and the abdominal visceral fat (P=0.013), respectively. A-1766G is approximately 2 kb downstream from the well-known A-3826G polymorphism, and no linkage between them was found (D'=0.929, R(2)=0.283). Three haplotypes (frequency >0.05) were examined from two polymorphisms and studied for their physiological effects. It was found that haplotype [GG] was significantly associated with increased body fat, while haplotype [GA] was associated with decreased body fat.

Adipose Tissue↗

PubMed2004

BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer.

In order to evaluate the role of BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer, 97 patients with sporadic breast cancer were analyzed for mutations in the BRCA1 and BRCA2 coding regions, by using a combination of fluorescent-conformation sensitive gel electrophoresis (F-CSGE) and direct sequencing. Fifty-five distinct sequence variants were detected, which included three pathogenic truncating mutations, 15 missense mutations, 16 polymorphisms, and 21 intronic variants. Twenty-six of these variants have never been previously reported and may be of Korean-specific origin. Two pathogenic BRCA1 mutations (c.922_924delinsT, c.5445G>A) and one pathogenic BRCA2 mutation (c.2259delT) were observed, and two of these (BRCA1 c.5445G>A and BRCA2 c.2259delT) are novel. The total prevalence of germline pathogenic mutations in BRCA1 and/or BRCA2 in Korean sporadic breast cancer is estimated to be about 3.1%. Considering that the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of germline BRCA mutations in sporadic breast cancer patients. Further study using a larger sample size is required to determine the merits of genetic diagnosis and counseling in breast cancer patients.

Adult↗

PubMed2004

Prevalence of BRCA1 and BRCA2 mutations in Korean breast cancer patients.

The incidence of breast cancer in Korea has been increasing in recent years, such that it is now the most common female cancer. Breast cancer in Korea is characterized by an earlier age of onset than in Western countries, suggesting that it would be related with genetic background. We assayed germline mutations in the BRCA genes to evaluate their genetic pathology in Korean breast cancer patients. The study subjects consisted of 173 patients at clinically higher risk and 109 unselected patients. Germline mutations in the entire coding sequences of the BRCA1 and BRCA2 genes were analyzed by Conformation-Sensitive Gel Electrophoresis (CSGE), and any aberrantly-sized band was sequenced. BRCA mutations were present in 12.7% of the high risk patients, compared with 2.8% of the unselected patients. Among high risk patients, mutations were most prevalent in patients with a family history of breast or first-degree ovarian cancer (22.1%), followed by those with male breast cancer (20%), bilateral breast cancer (20%), multiple organ cancer including breast (13%) and younger breast cancer patients (aged<35 yr) (8.1%). Moreover, BRCA mutations were detected in 34.8% of patients having two high risk factors. These findings suggest that BRCA gene mutation analysis should be performed on Korean patients with high-risk factors for breast cancer.

BRCA1 Protein↗

PubMed2003

Molecular chaperone GRP78/BiP interacts with the large surface protein of hepatitis B virus in vitro and in vivo.

The proper folding and assembly of viral envelope proteins are mediated by host chaperones. In this study, we demonstrated that an endoplasmic reticulum luminal chaperone GRP78/BiP bound specifically to the pre-S1 domain of the L protein in vitro and in vivo where complete viral particles were secreted, suggesting that GRP78/BiP plays an essential role in the proper folding of the L protein and/or assembly of viral envelope proteins.

Amino Acid Sequence↗