• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.299-304
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• 2014

Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.

• Investigative Magnetic Resonance Imaging
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• 제21권4호
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• pp.223-232
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• 2017

Purpose: To report the use of multiband accelerated echo-planar imaging (EPI) for resting-state functional MRI (rs-fMRI) to achieve rapid high temporal resolution at 3T compared to conventional EPI. Materials and Methods: rs-fMRI data were acquired from 20 healthy right-handed volunteers by using three methods: conventional single-band gradient-echo EPI acquisition (Data 1), multiband gradient-echo EPI acquisition with 240 volumes (Data 2) and 480 volumes (Data 3). Temporal signal-to-noise ratio (tSNR) maps were obtained by dividing the mean of the time course of each voxel by its temporal standard deviation. The resting-state sensorimotor network (SMN) and default mode network (DMN) were estimated using independent component analysis (ICA) and a seed-based method. One-way analysis of variance (ANOVA) was performed between the tSNR map, SMN, and DMN from the three data sets for between-group analysis. P < 0.05 with a family-wise error (FWE) correction for multiple comparisons was considered statistically significant. Results: One-way ANOVA and post-hoc two-sample t-tests showed that the tSNR was higher in Data 1 than Data 2 and 3 in white matter structures such as the striatum and medial and superior longitudinal fasciculus. One-way ANOVA revealed no differences in SMN or DMN across the three data sets. Conclusion: Within the adapted metrics estimated under specific imaging conditions employed in this study, multiband accelerated EPI, which substantially reduced scan times, provides the same quality image of functional connectivity as rs-fMRI by using conventional EPI at 3T. Under employed imaging conditions, this technique shows strong potential for clinical acceptance and translation of rs-fMRI protocols with potential advantages in spatial and/or temporal resolution. However, further study is warranted to evaluate whether the current findings can be generalized in diverse settings.

• The Korean Journal of Physiology and Pharmacology
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• 제12권2호
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• pp.83-87
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• 2008

The fyn-related kinase (FRK) belongs to the tyrosine kinase family of protein kinases. Recent studies have shown that Frk affects pancreatic beta cell number during embryogenesis and promotes beta cell cytotoxic signals in response to streptozotocin. To investigate the genetic association between FRK polymorphisms and the risk of obesity in Korean population, single nucleotide polymorphisms (SNPs) in the FRK gene region were selected and analyzed. The body mass index (BMI) was calculated, and biochemical data (systolic blood pressure, diastolic blood pressure, hemoglobin A1C, triglyceride, total cholesterol, high density lipoprotein, and low density lipoprotein) of blood sample from each subject were also measured. One hundred fifty five healthy control and 204 overweight/obesity subjects were recruited. Genotype frequencies of six SNPs [rs6568920 (+8391G>A), rs3756772 (+56780A>G), rs3798234 (+75687C>T), rs9384970 (+68506G>A), rs1933739 (+72978G>A), and rs9400883 (+75809A>G)] in the FRK gene were determined by Affymetrix Targeted Genotyping Chip data. According to the classification of Korean Society for the Study of Obesity, control (BMI 18 to < 23) and overweight/obesity (BMI$\geq$23) subjects were recruited. For the analysis of genetic data, EM algorithm, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was performed. Age and gender as covariates were adjusted. For biochemical data, Student's t test was used. The mean value of BMI in the control and overweigh/obesity groups was 21.1${\pm}$1.2 (mean${\pm}$SD) and 25.6${\pm}$2.0, respectively. All biochemical data of the overweight/obesity group were statistically significance, compared with the control group. Among six SNPs, two linkage disequilibrium (LD) blocks were discovered. One block consisted of rs1933739 and rs9400883, and the other comprised rs3756772 and rs3798234. One SNP (rs9384970, +68506G>A) showed an association with overweight/obesity in the codominant model (p=0.03). Interestingly, the AA genotype distribution in the overweight/obesity group (n=7, 3.5%) was higher than those in the control group (n=1, 0.6%), which is not found in either Japanese or Chinese subjects. Therefore, the AA genotype of rs9384970 may be a risk factor for development of obesity in Korean population. The results suggest that FRK may be associated with overweight/obesity in Korean population.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6269-6272
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• 2012

We conducted a case-control study to determine the association between several potential SNPs of excision repair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphisms in combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newly diagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>T and rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147 CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258 TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258 TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CC was associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findings suggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, but the effect needs to be further validated by larger sample size studies.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.763-767
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• 2014

Aim: To study the contribution of genetic variation in RAD51 to risk of esophageal squamous cell carcinoma (ESCC). Methods: Three single nucleotide polymorphisms (SNPs) in RAD51 (rs1801320, rs4144242 and rs4417527) were genotyped in 316 ESCC patients and 316 healthy controls in Anyang area of China using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Demographic variables between cases and controls were statistically compared by T test and Chi-square test. Hardy-Weinberg equilibrium was evaluated by the Chi-square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure any association with ESCC. Haplotype frequencies were estimated by Phase 2.1. Result: The genotype frequencies of rs1801320, rs4144242 and rs4417527 in patients with ESCC demonstrated no significant differences from those in control group (P>0.05). When the haplotypes of these three SNPs were constructed and their relationships with ESCC risk investigated, however, CGG was observed to increase the risk (P=0.020, OR=2.289). Conclusions: There was no association between the three SNPs of RAD51 and ESCC susceptibility in our Chinese population. However, the CGG haplotype might be a risk factor.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.548-553
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• 2010

목 적: IgA 신병증은 소아들의 만성 사구체 신염 중에서 가장 흔하게 일어나며, HLA유전자는 다양한 염증성 질환과 자가면역질환과 연관이 있어 왔다. 이 연구에서는 한국인에서 건강한 대조군과 IgA 신병증 환자군을 비교하여 IgA 신병증 발생 감수성 및 병리, 임상 양상과 $HLA-G$ 유전자의 SNP와의 연관성에 관해 알아보고자 하였다. 방 법: 소아 IgA 신병증을 앓고 있는 174명의 환자군과 438명의 정상 대조군에서 $HLA-G$ 유전자의 promoter SNP (rs1736936과 rs2735022)를 분석하고 비교하였다. 또한 IgA 신병증 환자들을 단백뇨($4mg/m^2/hour$ 이하군과 이상군)의 유무, 족세포 돌기의 소실 유무, 간질의 섬유화 및 세뇨관 위축이나 미만성 사구체 경화와 같은 병리학적 소견상 진행성 질환의 표지자유무에 따라 하위그룹으로 나누어 비교하였다. 결 과: IgA 신병증 환자군과 정상 대조군 간의 HLA-G에서의 SNP (rs1736936과 rs2735022) 빈도에 대한 유의한 차이는 발견되지 않았다. 또한 단백뇨의 유무, 족세포 돌기의 소실 유무, 질환의 병리학적 진행 정도을 의미하는 표지자의 유무와 SNP사이에서도 유의한 연관성을 보이지는 않았다. 그러나, 일체 배형으로서 rs1736936과 rs2735022는 소아 IgA 신병증을 일으키는 감수성에 대해 통계학적으로 유의한 연관성을 나타내었다(haplotype T/C: dominant model OR 1.71, 95% CI 1.00-2.92, $P$=0.049; haplotype C/T: recessive model OR 0.54, 95% CI 0.31-0.94, $P$=0.030). 결 론: 이번 연구에서 $HLA-G$ 유전자의 SNP 중 rs1736936와 rs2735022로 이루어진 일체배형과 IgA 신병증의 발생간에 유의한 관계를 관찰하였으며, IgA 신병증 환자들의 단백뇨 발생 유무, 족세포 돌기의 소실 유무 및 질병 진행 정도로 구분된 하위그룹과 후보 SNP들간의 유의한 관계는 확인할 수 없었다.

• Genomics & Informatics
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• 제8권4호
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• pp.206-211
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• 2010

The Fas (TNF receptor superfamily, member 6) (FAS)/FAS ligand (FASLG) interaction plays a central role in the regulation of programmed cell death. FAS and FASLG polymorphisms in promoter regions affect transcriptional activities. To investigate whether FAS and FASLG polymorphisms are associated with the development and clinical phenotypes of stroke, 2 promoter single nucleotide polymorphisms (SNPs) in FAS (rs1800682, -670C/T) and FASLG (rs763110, -844C/T) were selected and genotyped by direct sequencing in 220 stroke patients [107 ischemic stroke (IS), 77 intracerebral hemorrhage (ICH), and 36 subarachnoid hemorrhage (SAH)] and 369 control subjects. For the analysis of clinical symptoms, all stroke patients were divided into 3 clinical phenotypes according to the respective results of the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index (MBI) and the presence or absence of complex regional pain syndrome (CRPS). The SNPStats, SNPAnalyzer, and Helixtree programs were used to analyze the genetic data. Multiple logistic regression models (codominant, dominant, and recessive) were used to estimate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. The promoter SNP rs1800682 was associated with stroke in the codominant (OR=0.48, 95% CI=0.25-0.94, p=0.04) and dominant models (OR=0.51, 95% CI=0.30-0.87, p=0.011). However, a FASLG SNP (rs763110) was not in Hardy-Weinberg equilibrium (p<0.05). In the analysis of stroke types, rs1800682 was associated with IS in the codominant (OR=0.30, 95% CI=0.12-0.74, p=0.025), dominant (OR=0.44, 95% CI=0.23-0.88, p=0.018), and recessive models (OR=0.45, 95% CI=0.21-0.99, p=0.042). The genotype frequencies of rs1800682 were different between ICH and controls in the dominant model (OR=0.49, 95% CI=0.26-0.94, p=0.031) but not between SAH and controls. In the analysis of clinical symptoms, however, rs1800682 was not related to the 3 clinical phenotypes (NIHSS, MBI, and CRPS). These results suggest that a promoter SNP (rs1800682, -670C/T) in FAS may be associated with the development of stroke in the Korean population.

• Genomics & Informatics
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• 제6권3호
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• pp.110-116
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• 2008

Blood pressure refers to the force exerted by circulating blood on the walls of blood vessels, and chronical elevation of blood pressure is known as hypertension. Although hypertension is affected by genetic and environmental factors, the genetic background of hypertension is not fully understood. One of the candidate genetic factors, Prostaglandin-endoperoxide synthase 2 (PTGS2), is a membrane-bound enzyme, catalyzing the conversion of arachidonic acid to prostaglandin, and recently SNPs of PTGS2 gene was associated with hypertension in Japanese population. Therefore the association of PTGS2 polymorphisms was investigated with blood pressure in healthy Korean subjects, 470 unrelated individuals randomly selected from Ansung and Ansan cohorts. The 25 SNPs of PTGS2 gene were identified by the sequencing analysis of 24 Korean samples. Among identified polymorphisms, three SNPs (rs689466, -1329A>G; rs5275, +6365T>C; rs4648308, +8806G> A) were selected for further association analysis, and rs689466 located in promoter region was associated with blood pressure as well as triglyceride level in the blood. By in silico analysis, rs689466 locates in v-Myb transcription factor binding site, and the v-Myb site disappears when the SNP is changed from A to G nucleotide. Individuals with A/G and G/G genotype in rs689466 have higher blood pressure than those with A/A genotype, and the regression p-value is 0.008 for systolic and 0.004 for diastolic blood pressure. In summary, the PTGS2 polymorphism (rs689466) is associated with blood pressure in Asian populations based on this and Japanese studies, shedding light on it as a genetic risk marker of hypertension.

• Asian-Australasian Journal of Animal Sciences
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• 제4권1호
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• pp.91-97
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• 1991

Twenty five 75% Holstein Friesian cross bred bullocks fed rice straw (Oryza sativa) of long form, were fed with the following five treatments. 1. Rice straw, untreated (RS) 2. RS + water (1:1), stored for 24 hours (WRS) 3. RS (100 kg) + urea solution (4 kg urea/100 litre water) and dried (USRS) 4. RS (100 kg) + urea solution (as in 3) stored in wet condition for 24 hours (UWRS) 5. RS (100 kg) + urea solution (as in 3) stored in pit for 21 days (UTRS). Potential digestibility of treatments of RS was evaluated by monitoring (in vitro) Simulating Rumen like Fermentation (SRLF). The results indicated that Dry Matter Intake (DMI), digestibility of nutrients, N utilization were of the order UTRS > UWRS > USRS > WRS and RS (p < 0.05 to p < 0.01). SRLF index was high (255.84) for UTRS and least (145.58) for USRS. It was intermediary (199.66) for UWRS. The acetyl content (AC) of UTRS with higher hemicellulose (HCE) digestibility (80.8%) was low compared to UWRS, USRS, RS and WRS. The acetate content was of the order UTRS < UWRS < USRS < WRS and RS thereby indicating that reduction in acetyl content was an index of positive response of urea-treatment of RS. In addition, the ratio of HCE/AC in faeces of UTRS was 0.87 as against the ratios (2.26-2.48) observed in other treatments recording reduction in AC due to urea-treatment. Among the treatments, USRS only supplemented N while UTRS in addition to utilization N, increased the digestibility of structural carbohydrates. Reduction in treatment time from 21 days to 1 day (UWRS) resulted in improvements similar to those of UTRS.

• Asian-Australasian Journal of Animal Sciences
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• 제30권2호
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• pp.181-186
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• 2017

Objective: Leucaena leucocephala (Leucaena) is a perennial tropical legume that can be directly grazed or harvested and offered to ruminants as hay, silage, or fresh. However, Leucaena contain phenolic compounds, which are considered anti-nutritional factors as these may reduce intake, digestibility and thus animal performance. Therefore, the objective of this experiment was to determine effects of Leucaena silage (LS) feeding levels on rumen microbial populations, N-balance and microbial protein synthesis in dairy steers. Methods: Four, rumen fistulated dairy steers with initial weight of $167{\pm}12kg$ were randomly assigned to receive dietary treatments according to a $4{\times}4$ Latin square design. Treatments were as followings: T1 = untreated rice straw (RS; Control), T2 = 70% RS+30% LS, T3 = 40% RS+60% LS, and T4 = 100% LS. Dairy steers were fed rice straw and LS ad libitum and supplemented with concentrate at 0.2% of body weight/d. Results: Results revealed that the rumen microbial population, especially cellulolytic, proteolytic bacteria and fungal zoospores were enhanced in steers that received 60% of LS (p<0.05), whereas the amylolytic bacteria population was not affected by treatments (p>0.05). Protozoal population was linearly decreased with increasing level of LS (p<0.05). Moreover, N-balance and microbial protein synthesis were enhanced by LS feeding (p<0.05) and were the highest in 60% LS group. Conclusion: Based on this study, it could be concluded that replacement of RS with 60% LS significantly improved microbial population and microbial protein synthesis in diary steers.