• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2311-2314
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• 2012

Genetic polymorphisms of uridine diphosphate-glucuronosyltransferases 1A6 (UGT1A6) and 1A7 (UGT1A7) may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interaction between polymorphisms of these repair genes and tobacco smoking in colorectal cancer (CRC). A total of 68 individuals with CRC and 112 non-cancer controls were divided into non-smoker and smoker groups according to pack-years of smoking. Genetic polymorphisms of UGT1A6 and UGT1A7 were examined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found a weak association of UGT1A6 polymorphisms with CRC risk (crude odds ratio [OR], 1.65;95% confidence interval [95% CI], 0.9-3.1, P=0.107; adjusted OR 1.95%, 95% CI 1.0-3.8, P=0.051). The ORs for the UGT1A7 polymorphisms were statistically significant (crude OR: 26.40, 95% CI: 3.5-198.4, P=0.001; adjusted OR: 21.52, 95% CI: 2.8-164.1, P=0.003). The joint effect of tobacco exposure and UGTIA6 polymorphisms was significantly associated with colorectal cancer risk in non-smokers (crude OR, 2.11; 95% CI, 0.9-5.0, P=0.092; adjusted OR 2.63, 95% CI, 1.0-6.7, P=0.042). In conclusion, our findings suggest that UGT1A6 and UGT1A7 gene polymorphisms are associated with CRC risk in the Japanese population. In particualr, UGT1A6 polymorphisms may strongly increase CRC risk through the formation of carcinogens not associated with smoking.

• Animal Bioscience
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• v.36 no.4
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• pp.570-583
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• 2023

Objective: Fibroblast growth factors (FGFs) play critical roles in embryo development, and immune responses to infectious diseases. In this study, to investigate the roles of FGFs, we performed genome-wide identification, expression, and functional analyses of FGF family members in chickens. Methods: Chicken FGFs genes were identified and analyzed by using bioinformatics approach. Expression profiles and Hierarchical cluster analysis of the FGFs genes in different chicken tissues were obtained from the genome-wide RNA-seq. Results: A total of 20 FGF genes were identified in the chicken genome, which were classified into seven distinct groups (A-F) in the phylogenetic tree. Gene structure analysis revealed that members of the same clade had the same or similar exon-intron structure. Chromosome mapping suggested that FGF genes were widely dispersed across the chicken genome and were located on chromosomes 1, 4-6, 9-10, 13, 15, 28, and Z. In addition, the interactions among FGF proteins and between FGFs and mitogen-activated protein kinase (MAPK) proteins are limited, indicating that the remaining functions of FGF proteins should be further investigated in chickens. Kyoto encyclopedia of genes and genomes pathway analysis showed that FGF gene interacts with MAPK genes and are involved in stimulating signaling pathway and regulating immune responses. Furthermore, this study identified 15 differentially expressed genes (DEG) in 21 different growth stages during early chicken embryo development. RNA-sequencing data identified the DEG of FGFs on 1- and 3-days post infection in two indigenous Ri chicken lines infected with the highly pathogenic avian influenza virus H5N1 (HPAIV). Finally, all the genes examined through quantitative real-time polymerase chain reaction and RNA-Seq analyses showed similar responses to HPAIV infection in indigenous Ri chicken lines (R² = 0.92-0.95, p<0.01). Conclusion: This study provides significant insights into the potential functions of FGFs in chickens, including the regulation of MAPK signaling pathways and the immune response of chickens to HPAIV infections.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6783-6787
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• 2015

Background: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understanding the current state of evidence in this area and its limitations is important for the care of patients who require endocrine therapy for breast cancer. Materials and Methods: A total of 101 patients with breast cancer who received tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene by nested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neu status, and stage 3. Results: The mean age of the patients with the disease recurrence was $50.8{\pm}6.4$ and in non recurrent patients was $48.2{\pm}6.8$. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifen-treated patients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women with breast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreased likelihood of recurrence. Conclusions: This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.659-668
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• 1993

Background: p53 is currently considered as a tumor suppressive gene product, and its alterations are suggested to be involved in several human malignancies, including non-small cell lung cancers. p53 expression rates are variable in many reports and among cell types. Also, whether the phase of p53 expression is early or late during carcinogenesis is not certain. Thus, We have investigated to evaluate p53 expression rates of the various cell types and tissues and identify expression phase (early or late). Method: We obtained 71 tissue from 50 non-small cell lung cancer patients and performed the simple immunohistochemical staining using nonspecific monoclonal antibody(NCL-p53DO7). Results: 1) In non-small cell lung cancer patients. the expression rate of lungs(46.5%) is higher than that(25.0%) of lymph nodes. But, there is no significant difference between two groups. 2) Among the various cell types, p53 expression rates in squamous cell carcinoma and adenocarcinoma are 58.3% and 50.0% respectively without significant difference. 3) p53 expression rates in various stages are 33.3%, 60.0%, 40.0%, 60.0% and 66.7% in stage I, II, IIIa, IIIb and IV, respectively with no significant difference. 4) p53 expression rates in the various T parameters are 33.3%, 50.0%, 16.7% and 100% in T1, T2, T3 and T4, respectively and p53 expression rates in the various N parameters are 27.3%, 22.2% and 25.0% in N1, N2 and N3, respectively. There are no significant differences in the expression rates among varous T & N parameters. 5) p53 expression rates of lymph nodes in patients who have positive stains in lungs are 12.5% and 50.0% in N1 and N2. 6) p53 expression rates of all lymph nodes in patients who have negative stains in lungs are 0.0%. Conclusion: The above results show that p53 expression rate in non-small cell lung cancers is not correlated with cell type and progression of stage and it is thought to need further investigations about at what phase p53 expression influences the development and progression of lung cancers.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.18-25
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• 2004

Purpose : Alport syndrome is clinically characterized by hereditary progressive nephritis causing ESRD with irregular thickening of the GBM and sensory neural hearing loss. The mutations of type IV collagen gene(COL4A5) located on the long arm of X chromosome is considered responsible for most of the structural abnormalities in the GBM of Alport patients. Since no definite clinical prognostic predictor has been reported in the disease yet, we designed this study to evaluate the significance of genetic polymorphism of the angiotensin converting enzyme in children with Alport syndrome as a prognostic factor for disease progression. Methods : ACE I/D genotype were examined by PCR amplification of the genomic DNA in 12 patients with Alport syndrome and 12 of their family members. Alport patients were divided into two groups; the conservative group, those who had preserved renal function for more than 10 years of age, the early CRF group, those who had progressed to CRF within 10 years of age. Results : The mean age of onset was $3.45{\pm}2.4$ years in the conservative group, $4.4{\pm}1.2$ years in the early CRF group. Sex ratios were 5:3 and 2:1 in each group. Among 12 cases of patients, 4 cases were in early CRF group and their mean duration of onset to CRF was 4.5 yews(8.9 years of age). Eight patients(67%) were in the conservative group and they had normal renal function for more than 10 years of age(mean duration of renal preservation was 10.6 years). The incidence of II type ACE gene were in 25.0%(3 cases), ID type in 41.7%(5 cases), DD type in 33.3%(4 cases). There was no significant difference between Alport patient and normal control(II type 44.3%, ID type 40.9%, DD type 14.8%). The incidence of DD type of early CRF group were higher than that of the conservative group(75% vs 12.5%)(p<0.05). There was no difference in ACE gene polymorphism between normal Alport family members and control group. Conclusion : Even though there was no significant difference of ACE polymorphism between Alport patients and the normal control group, the incidence of DD type is significantly increased in early CRF group which means DD type of ACE polymorphism has a possibility of being a predictor for early progression to CRF in Alport patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.724-728
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• 2002

Angiotensin-converting enzyme (ACE) gene polymorphism, which consists of presence (insertion, I) or absence (deletion, D) of a 250-bp fragment, is associated with ischemic heart disease, renovascular disease, systemic lupus erythematosus. Subjects with the DD genotype have higher levels of circulating ACE than subjects with the II genotype and show an increased tendency towards vascular wall thickness and contribute to the development of vascular disease. But the association between I/D polymorphism of the ACE gene and cerebrovascular disease is still controversial. The aim of this study was to determine whether the DNA polymorphism of the ACE are associated with cerebrovascular disease in Korean population. The study group comprised 377 Korean patients admitted to Kyunghee Oriental Medical Center in the year of 2000 for the treatment of brain infarction or brain hemorrhage. Magnetic resonance imaging(MRI) was performed for each patient to determine the stroke phenotype, infarction or hemorrhage. The 183 subjects without evidence of brain infarction or brain hemorrhage were selected from the some ethnical population(control group). Venous blood samples were drawn from each subject for the extraction of DNA. Genotypes of ACE were determined by polymerase chain reaction amplification of the genomic DNA. Case and control genotype frequencies were compared by chi-square testing. Both the patients and the controls were classified respectively into 4 groups: age less than forty years, age forty one to fifty, age fifty one to sixty, age greater than sixty years. There were no significant differences in the distributions of ACE genotypes among the patients with infarction, with hemorrhage and controls (Infarction: D/D 15.8%, I/D 46.7%, I/I 37.5%, Hemorrhage: D/D 15.1%, I/D 46.5%, I/I 38.4%, Control: D/D 18.6%, I/D 50.3%, I/I 31.2%). There was a significant difference in the distribution of ACE genotypes between the age greater than sixty year subgroup of patient with brain hemorrhage and the control (Hemorrhage: D/D 0%, I/D 55.6%, I/I 44.4%, Control: D/D 13.0%, I/D 63.0%, I/I 23.9%; Pearson Chi-Square value 5.956, P<0.05). Furthermore, the frequency of the ACE D/D type declined with increasing age both in the patient and control group (Patient group: age < 50 D/D 21.5%, age > 50 D/D 14.42%; Control group: age < 50 D/D 21.0%, age > 50 D/D 14.2%). In conclusion there is no clear association between ACE polymorphism and cerebrovascular disease in Korean population. Although, there was a tendency for the frequency of the ACE D/D type declined with increasing age in both patients and controls.

• Clinical and Experimental Pediatrics
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• v.50 no.6
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• pp.556-564
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• 2007

Purpose : We hypothesized that the persisting bronchial hyperresponsiveness (BHR) of adolescents with asthma remission may be controlled mainly by genetic factors, and the BHR of symptomatic asthma by airway inflammation. ${\beta}_2$-adrenoceptor gene is considered to be a candidate gene in the development of BHR. Thus, ${\beta}_2$-adrenoceptor gene polymorphism may be associated with the BHR of adolescents with asthma remission, but not with the BHR of symptomatic asthma. To evaluate this hypothesis, ${\beta}_2$-adrenoceptor gene polymorphism at 2 sites (Arg16-Gly, Gln27-Glu) were examined. Methods : Two hundred two adolescents with BHR ($PC_{20}<18\;mg/mL$) and long term remission (neither asthma-related symptoms nor medication during the previous 2 years) of their asthma (remission group), 182 adolescents with symptomatic asthma (symptomatic group), and 200 healthy adolescents (control group) were studied. Asthma phenotypes were determined using methacholine bronchial provocation test and skin prick test. Genotypes of ${\beta}_2$-adrenoceptor polymorphism were evaluated by PCR-based methods. Results : Gly/Gly allele and Gly16-Gln27 haplotype were more prevalent in the remission group than in the control group (P=0.01, P=0.02), although there was no difference between the symptomatic group and the control group. In the remission group, there was significant difference in geometric mean of $PC_{20}$ among the 3 groups subdivided by the number of Gly16-Gln27 haplotype, showing that the Gly16-Gln27 haplotype was positively associated with BHR. However, no association was found between Gly16-Gln27 haplotype and BHR in the symptomatic group. Conclusion : This study demonstrates that ${\beta}_2$-adrenoceptor polymorphism at amino acid 16 and 27 was associated with BHR persisting in adolescents with asthma remission.

• 한국균학회소식:학술대회논문집
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• 2015.05a
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• pp.53-53
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• 2015

Agrobacterium tumefaciens-mediated transformation(ATMT) of Flammulina velutipes was used to produce a diverse number of transformants to discover the functions of gene that is vital for its variation color, spore pattern and cellulolytic activity. Futhermore, the transformant pool will be used as a good genetic resource for studying gene functions. Agrobacterium-mediated transformation was conducted in order to generate intentional mutants of F. velutipes strain KACC42777. Then Agrobacterium tumefaciens AGL-1 harboring pBGgHg was transformed into F. velutipes. This method is use to determine the functional gene of F. velutipes. Inverse PCR was used to insert T-DNA into the tagged chromosomal DNA segments and conducting sequence analysis of the F. velutipes. But this experiment had trouble in diverse morphological mutants because of dikaryotic nature of mushroom. It needed to make monokaryotic fruiting varients which introduced genes of compatible mating types. In this study, next generation sequencing data was generated from 28 strains of Flammulina velutipes with different phenotypes using Illumina Hiseq platform. Filtered short reads were initially aligned to the reference genome (KACC42780) to construct a SNP matrix. And then we built a phylogenetic tree based on the validated SNPs. The inferred tree represented that white- and brown- fruitbody forming strains were generally separated although three brown strains, 4103, 4028, and 4195, were grouped with white ones. This topological relationship was consistently reappeared even when we used randomly selected SNPs. Group I containing 4062, 4148, and 4195 strains and group II containing 4188, 4190, and 4194 strains formed early-divergent lineages with robust nodal supports, suggesting that they are independent groups from the members in main clades. To elucidate the distinction between white-fruitbody forming strains isolated from Korea and Japan, phylogenetic analysis was performed using their SNP data with group I members as outgroup. However, no significant genetic variation was noticed in this study. A total of 28 strains of Flammulina velutipes were analyzed to identify the genomic regions responsible for producing white-fruiting body. NGS data was yielded by using Illumina Hiseq platform. Short reads were filtered by quality score and read length were mapped on the reference genome (KACC42780). Between the white- and brown fruitbody forming strains. There is a high possibility that SNPs can be detected among the white strains as homozygous because white phenotype is recessive in F. velutipes. Thus, we constructed SNP matrix within 8 white strains. SNPs discovered between mono3 and mono19, the parental monokaryotic strains of 4210 strain (white), were excluded from the candidate. If the genotypes of SNPs detected between white and brown strains were identical with those in mono3 and mono19 strains, they were included in candidate as a priority. As a result, if more than 5 candidates SNPs were localized in single gene, we regarded as they are possibly related to the white color. In F. velutipes genome, chr01, chr04, chr07,chr11 regions were identified to be associated with white fruitbody forming. White and Brown Fruitbody strains can be used as an identification marker for F. veluipes. We can develop some molecular markers to identify colored strains and discriminate national white varieties against Japanese ones.

• Korean Journal of Poultry Science
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• v.36 no.1
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• pp.39-45
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• 2009

This study was carried out to investigate the effect of dietary supplementation of Acanthopanax (A) senticosus and Eucommiaceae on the expression of lipogenic, myogenic and oxidative stress genes in broiler chickens. Birds were subjected (assigned) to one of the following 5 dietary treatments: control (CON), A. senticosus 0.5% (T1), 1.0% (T2), Eucommiaceae 0.5% (T3) and 1% (T4). Each treatment was replicated 8 times with 4 birds per replication, housed in 4 birds per cage. Birds were arranged according to randomized block design. Feeding trial was conducted from day 4 to 35th day of age. Liver and muscle tissues were collected for analysis. Broilers subjected to 1% A. senticosus had higher feed conversion ratio than the other treated birds whereas no significant differences were found in body weight, weight gain and feed intake. The gene expression levels of fatty acid synthase were not different among the treatments while the transcription factor $PPAR{\gamma}$ was highly expressed in Eucommiaceae but not in control and A. senticosus. The gene expression levels of myogenin were high in both A. senticosus and Eucommiaceae compared to control group. MyoD also showed high expression in treated groups furthermore, Eucommiaceae stimulated the expression of MyoD more than that of A. senticosus. The antioxidant gene expressions (SOD, CAT, SOD, GPX) generally were not much different among the treatments, however, SOD and GPX were stimulated in broilers consumed 1% Eucommiaceae diet. The result of this experiment showed that dietary supplementation of A. senticosus and Eucommiaceae in broiler may improve the antioxidant defence system through SOD and GPX without affect of growth performance in broilers.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.193-200
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• 2005

Purpose : An atrophic renal scar(RS) is one of the underlying causes for childhood hyper tension and chronic renal failure. The risk factors for atrophic renal scar were evaluated. Methods : 41 children, who presented with first febrile urinary tract Infection at the Ewha Womans University Hospital between 1995 and 2003 and had generalized atrophic RS on $^{99m}Tc-DMSA$ renal scan, were retrospectively studied. Atrophic RS was divided into severe atrophic RS(n=14) if relative uptake on renal scan was below 10$\%$, or mild atrophic RS(n=27) if relative uptake on renal scan was between 10-35$\%$. RS was defined as congenital if the scar was detected on the first renal scan, and as acquired if the scar developed on the follow-up renal scan from acute pyelonephritis of the first renal scan. The control group was consisted of randomly selected 41 children with segmental RS. The risk factors for atrophic RS such as the generation time, VUR, gender and ACE gene polymorphism were evaluated. Results : The age distribution of atrophic RS and segmental RS did not differ significantly (P>0.05). The rate of congenital RS in atrophic RS was 61.0$\%$(25/41), which was significantly higher than 9.8$\%$(4/41) of segmental RS(P<0.01). Atrophic RS developed mote frequently in male children(M:F 68.3$\%$ 31.7$\%$) than segmental RS(M:F 41.4$\%$ .58.5$\%$)(P<0.05). Vesicoureteral reflux(VUR) was found in 92.7$\%$(38/41) of 4he atrophic RS, which was significantly higher than 53.7$\%$(22/41) of segmental RS(P<0.05). In children without VUR, the male to female ratio did not differ between atrophic RS and segmental RS(P>0.05) But in children with VUR, there was a higher proportion of males with severe atrophic RS than segmental RS($85.7\%:45.5\%$) ACE gene polymorphism did not differ between the atrophic and segmental RS groups, irrespective of the presence of VUR(P>0.05). Conclusion : Most atrophic RSs were congenital which could not be preventable postnatally and the major risk factors were VUR and the male gender. ACE gene polymorphism was not the significant risk factor for an atrophic RS. (J Korean Soc Pedialr Nephrol 2005;9:193-200)