• Title/Summary/Keyword: gene carrier

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Association Between p53 codon 72 Polymorphism and Cervical Cancer Risk Among Asians: a Huge Review and Meta-analysis

  • Zhou, Xin;Gu, Yang;Zhang, Shu-Lan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4909-4914
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    • 2012
  • Objective: The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of the association between p53 codon 72 polymorphism (Arg72Pro, rs1042522 G>C) and cervical cancer risk among Asians. Methods: A literature search of Pubmed, Embase, Web of Science and CBM databases from inception through June 2012 was conducted. The meta-analysis was performed using STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association. Twenty-eight case-control studies were included with a total of 3,580 cervical cancer cases and 3,827 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed that the Pro/Pro genotype was associated with increased risk of cervical cancer under the heterozygous model (Pro/Pro vs. Arg/Pro: OR = 1.25, 95%CI: 1.02-1.53, P= 0.005). However, no statistically significant associations were found under four other genetic models (Pro vs. Arg: OR = 0.97, 95%CI: 0.85-1.10, P= 0.624; Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 0.84, 95%CI: 0.70-1.01, P= 0.058; Pro/Pro vs. Arg/Arg + Arg/Pro: OR = 1.13, 95%CI: 0.92-1.39, P= 0.242; Pro/Pro vs. Arg/Arg: OR = 0.97, 95%CI: 0.76-1.22, P= 0.765; respectively). In the subgroup analysis based on country, the Pro/Pro genotype and Pro carrier showed significant associations with increased risk of cervical cancer among Indian populations, but not among Chinese, Japanese and Korean populations. Conclusion: Results from the current meta-analysis suggests that p53 codon 72 polymorphism might be associated with increased risk of cervical cancer, especially among Indians.

What Made Her Give Up Her Breasts: a Qualitative Study on Decisional Considerations for Contralateral Prophylactic Mastectomy among Breast Cancer Survivors Undergoing BRCA1/2 Genetic Testing

  • Kwong, Ava;Chu, Annie T.W.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2241-2247
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    • 2012
  • Objective: This qualitative study retrospectively examined the experience and psychological impact of contralateral prophylactic mastectomy (CPM) among Southern Chinese females with unilateral breast cancer history who underwent BRCA1/2 genetic testing. Limited knowledge is available on this topic especially among Asians; therefore, the aim of this study was to acquire insight from Chinese females' subjective perspectives. Methods: A total of 12 semi-structured in-depth interviews, with 11 female BRCA1/BRCA 2 mutated gene carriers and 1 non-carrier with a history of one-sided breast cancer and genetic testing performed by the Hong Kong Hereditary Breast Cancer Family Registry, who subsequently underwent CPM, were assessed using thematic analysis and a Stage Conceptual Model. Breast cancer history, procedures conducted, cosmetic satisfaction, pain, body image and sexuality issues, and cancer risk perception were discussed. Retrieval of medical records using a prospective database was also performed. Results: All participants opted for prophylaxis due to their reservations concerning the efficacy of surveillance and worries of recurrent breast cancer risk. Most participants were satisfied with the overall results and their decision. One-fourth expressed different extents of regrets. Psychological relief and decreased breast cancer risk were stated as major benefits. Spouses' reactions and support were crucial for post-surgery sexual satisfaction and long-term adjustment. Conclusions: Our findings indicate that thorough education on cancer risk and realistic expectations of surgery outcomes are crucial for positive adjustment after CPM. Appropriate genetic counseling and pre-and post-surgery psychological counseling were necessary. This study adds valuable contextual insights into the experiences of living with breast cancer fear and the importance of involving spouses when counseling these patients.

Construction of a High-Quality Yeast Two-Hybrid Library and Its Application in Identification of Interacting Proteins with Brn1 in Curvularia lunata

  • Gao, Jin-Xin;Jing, Jing;Yu, Chuan-Jin;Chen, Jie
    • The Plant Pathology Journal
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    • v.31 no.2
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    • pp.108-114
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    • 2015
  • Curvularia lunata is an important maize foliar fungal pathogen that distributes widely in maize growing area in China, and several key pathogenic factors have been isolated. An yeast two-hybrid (Y2H) library is a very useful platform to further unravel novel pathogenic factors in C. lunata. To construct a high-quality full length-expression cDNA library from the C. lunata for application to pathogenesis-related protein-protein interaction screening, total RNA was extracted. The SMART (Switching Mechanism At 5' end of the RNA Transcript) technique was used for cDNA synthesis. Double-stranded cDNA was ligated into the pGADT7-Rec vector with Herring Testes Carrier DNA using homologous recombination method. The ligation mixture was transformed into competent yeast AH109 cells to construct the primary cDNA library. Eventually, a high qualitative library was successfully established according to an evaluation on quality. The transformation efficiency was about $6.39{\times}10^5$ transformants/$3{\mu}g$ pGADT7-Rec. The titer of the primary cDNA library was $2.5{\times}10^8cfu/mL$. The numbers for the cDNA library was $2.46{\times}10^5$. Randomly picked clones show that the recombination rate was 88.24%. Gel electrophoresis results indicated that the fragments ranged from 0.4 kb to 3.0 kb. Melanin synthesis protein Brn1 (1,3,8-hydroxynaphthalene reductase) was used as a "bait" to test the sufficiency of the Y2H library. As a result, a cDNA clone encoding VelB protein that was known to be involved in the regulation of diverse cellular processes, including control of secondary metabolism containing melanin and toxin production in many filamentous fungi was identified. Further study on the exact role of the VelB gene is underway.

Establishment of a diagnostic method for porcine proliferative enteropathy using polymerase chain reaction (중합효소연쇄반응을 이용한 돼지 증식성 장염 진단기법 확립)

  • Lym, Suk-kyung;Lee, Hee-soo;Woo, Sung-ryong;Yoon, Soon-seek;Moon, Oun-kyong;Lee, Yoo-young;Koh, Hong-bum
    • Korean Journal of Veterinary Research
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    • v.39 no.1
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    • pp.118-125
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    • 1999
  • Porcine Proliferative Enteropathy(PPE) is an infectious enteric disease and a major cause of economic loss in swine industry due to weight loss, poor growth and sudden death in growing and finishing pigs at 6 to 20 weeks of age. PPE has been diagnosed by clinical signs, syndrom and lesions in the intestine in Korea. However, the diagnostic method had several problems in the detection of infected or carrier pigs. Therefore, in this study, we established the polymerase chain reaction(PCR) which was a fast, specific and sensitive method for identification of Lawsonia intracellularis (L intracellularis). We designed and synthesized primer on the 16S rDNA and p78 gene encoding L intracellularis. Specificity of the method was confirmed by comparison of the PCR results using other enteric bacteria and the study has shown that PCR method was sensitive to detect 1ng of genomic DNA as a template. Identity of the PCR products was confirmed by comparison of pattern of restriction endonuclease analysis with restriction enzyme Hae III and Pst I. Also, the PCR method was applicable to the naturally affected pigs with PPE. Based on the results from this study, the PCR method could be used as a fast and specific diagnostic tool for PPE.

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Triclosan Resistance in a Bacterial Fish Pathogen, Aeromonas salmonicida subsp. salmonicida, is Mediated by an Enoyl Reductase, FabV

  • Khan, Raees;Lee, Myung Hwan;Joo, Haejin;Jung, Yong-Hoon;Ahmad, Shabir;Choi, Jinhee;Lee, Seon-Woo
    • Journal of Microbiology and Biotechnology
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    • v.25 no.4
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    • pp.511-520
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    • 2015
  • Triclosan, the widely used biocide, specifically targets enoyl-acyl carrier protein reductase (ENR) in the bacterial fatty acid synthesis system. Although the fish pathogen Aeromonas salmonicida subsp. salmonicida exhibits triclosan resistance, the nature of this resistance has not been elucidated. Here, we aimed to characterize the triclosan resistance of A. salmonicida subsp. salmonicida causing furunculosis. The fosmid library of triclosan-resistant A. salmonicida subsp. salmonicida was constructed to select a fosmid clone showing triclosan resistance. With the fosmid clone showing triclosan resistance, a subsequent secondary library search resulted in the selection of subclone pTSR-1. DNA sequence analysis of pTSR-1 revealed the presence of a chromosomal-borne fabV-encoding ENR homolog. The ENR of A. salmonicida (FabVas) exhibited significant homology with previously known FabV, including the catalytic domain YX(8)K. fabVas introduction into E. coli dramatically increased its resistance to triclosan. Heterologous expression of FabVas might functionally replace the triclosan-sensitive FabI in vivo to confer E. coli with triclosan resistance. A genome-wide search for fabVas homologs revealed the presence of an additional fabV gene (fabVas2) paralog in A. salmonicida strains and the fabVas orthologs from other gram-negative fish pathogens. Both of the potential FabV ENRs expressed similarly with or without triclosan supplement. This is the first report about the presence of two potential FabV ENRs in a single pathogenic bacterium. Our result suggests that triclosan-resistant ENRs are widely distributed in various bacteria in nature, and the wide use of this biocide can spread these triclosan-tolerant ENRs among fish pathogens and other pathogenic bacteria.

Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE) Cohorts

  • Shim, Unjin;Kim, Han-Na;Sung, Yeon-Ah;Kim, Hyung-Lae
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.195-202
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    • 2014
  • Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, $52.2{\pm}8.9years$ ; body mass index, $24.6{\pm}3.2kg/m^2$). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < $5{\times}10^{-6}$), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < $1.38{\times}10^{-7}$, Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

Dopamine D2 Receptor Gene TaqI A Polymorphism in Korean Social Phobia Patients : Preliminary Study (한국인 사회공포증 환자에서 도파민 D2 수용체 TaqI A 유전자 다형성 : 예비적 연구)

  • Kim, Bum-Jo;Lim, Se-Won;Shin, Dong-Won;Oh, Kang-Seob;Lee, Min-Soo
    • Korean Journal of Biological Psychiatry
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    • v.14 no.2
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    • pp.106-114
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    • 2007
  • Objective : It is suggested that disturbance of dopaminergic system might be related to the possible mechanism of social phobia. The aim of this study was to investigate the possible association of DRD2 TaqI polymorphism and social phobia. Method : Fifty-one patients with social phobia and 200 comparison subjects were tested for DRD2 TaqI A polymorphism. The severity of social phobic symptoms was measured by self-report version of the Liebowitz Social Anxiety Scale(LSAS-SR) and Hamilton anxiety scale(HAM-A). Results : There was no signigicant difference in the genotype, allele frequency, A1 carrier frequency, and heterozygote frequency DRD2 TaqI A polymorphism between the social phobia patients and the control groups. However, we found significant decrease in somatic anxiety of the HAM-A in the patients having A2A2 homozygotes(p=0.014). In addition, patients having A1A2 heterozygotes showed more anxiety in two subscales (p=0.042 in anxiety, p=0.019 in performance) of the LSAS-SR. Conclusion : These results suggest that DRD2 A2 homozygote might have a protective role against somatic anxiety, and molecular heterosis of DRD2 TaqI A polymorphism might be related with more severe anxiety in social phobia.

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Effect of Molecular Weights of Polyethyleneimine on the Polyplex Formation with Calf Thymus DNA

  • Cho, Tae-Sub;Jungho Han;Kim, Seog K.;Lee, Jae-Cheol
    • Macromolecular Research
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    • v.12 no.3
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    • pp.276-281
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    • 2004
  • In this study we investigated the spectral properties, including electric absorption, circular and linear dichroism (CD and LD), and fluorescence emission, of DNA in a DNA-branched polyethyleneimine (BPEI) polyplex at various polymer molecular weights (M$\_$w/) and BPEI-amine-to-DNA-phosphate ratios (N/P ratios). All BPEIs exhibited a common N/P dependence in their absorption and CD spectra. At N/P ratios < 1.0, we observed some hyperchromism in the absorption spectrum, red-shifts in CD bands, and decreases in LD intensity and fluorescence intensity of intercalated ethidium. At intermediate N/P ratios, complete collapse of all spectra occurred. As the N/P ratio increased further, the polyplex dissolved in water. From its characteristic CD spectrum obtained under these conditions, we conclude that the DNA exists in a B-like form. The fluorescence and LD intensities never recovered even at high N/P ratios- which indicates that the dissolved polyplex possesses positive charges and the DNA in the polyplex is condensed despite its B-form CD spectrum. The N/P range in which the absorption and CD signals collapsed was wider when the BPEIs M$\_$w/ decreased. In the case where the BPEIs M$\_$w/ was 0.8 k, recovery of the absorption and CD spectral properties at a high N/P ratio was never achieved, which suggests that the molecular weight of the polymer plays an important role in its dissolution at a high N/P ratio.

Intratumoral Administration of Rhenium-188-Labeled Pullulan Acetate Nanoparticles (PAN) in Mice Bearing CT-26 Cancer Cells for Suppression of Tumor Growth

  • Song, Ho-Chun;Na, Kun;Park, Keun-Hong;Shin, Chan-Ho;Bom, Hee-Seung;Kang, Dong-Min;Kim, Sung-Won;Lee, Eun-Seong;Lee, Don-Haeng
    • Journal of Microbiology and Biotechnology
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    • v.16 no.10
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    • pp.1491-1498
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    • 2006
  • The feasibility of pullulan acetate nanoparticles (PAN) with ionic strength (IS) sensitivity as a radioisotope carrier to inhibit tumor growth is demonstrated. PAN was radiolabeled with rhenium 188 (Re-188) without any chelating agents. The labeling efficiency of Re-188 into PAN (Re-188PAN) was $49.3{\pm}4.0%$ as determined by TLC. The tumor volumes of mice treated with 0.45 mCi of Re-188-PAN were measured and compared with that of free Re-188 after 5 days of intratumoral injection. For the histological evaluation of apoptotic nuclei of tumor cells, hematoxylin and eosin (H&E), and terminal deoxynucleotidyl transferase biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed. The mean tumor volume of the Re-188-PAN-treated group was decreased by 36% after 5 days, whereas that the free Re-188-treated group was decreased by only 15% (P<0.05). The mean number of TUNEL-positive cells in Re-188-PAN-treated tumors at $144.3{\pm}79.9$ cells/section was significantly greater than the control ($26.7{\pm}7.9$ cells/section, P=0.03). The numbers of leukocyte and lymphocyte were decreased in both free Re-188- and Re-188-PAN-treated mice. These results indicated that the intratumoral injection of Re-188-PAN effectively inhibits the tumor growth by prolonging Re-188 retention time in tumor site induced by the IS sensitivity.

Polymorphisms of SLC22A9 (hOAT7) in Korean Females with Osteoporosis

  • Ahn, Seong Kyu;Suh, Chang Kook;Cha, Seok Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.4
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    • pp.319-325
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    • 2015
  • Among solute carrier proteins, the organic anion transporters (OATs) play an important role for the elimination or reabsorption of endogenous and exogenous negatively charged anionic compounds. Among OATs, SLC22A9 (hOAT7) transports estrone sulfate with high affinity. The net decrease of estrogen, especially in post-menopausal women induces rapid bone loss. The present study was performed to search the SNP within exon regions of SLC22A9 in Korean females with osteoporosis. Fifty healthy controls and 50 osteoporosis patients were screened for the genetic polymorphism in the coding region of SLC22A9 using GC-clamped PCR and denaturing gradient gel electrophoresis (DGGE). Six SNPs were found on the SLC22A9 gene from Korean women with/without osteoporosis. The SNPs were located as follows: two SNPs in the osteoporosis group (A645G and T1277C), three SNPs in the control group (G1449T, C1467T and C1487T) and one SNP in both the osteoporosis and control groups (G767A). The G767A, T1277C and C1487T SNPs result in an amino acid substitution, from synonymous vs nonsynonymous substitution arginine to glutamine (R256Q), phenylalanine to serine (F426S) and proline to leucine (P496L), respectively. The Km values and Vmax of the wild type, R256Q, P496L and F426S were 8.84, 8.87, 9.83 and $12.74{\mu}M$, and 1.97, 1.96, 2.06 and 1.55 pmol/oocyte/h, respectively. The present study demonstrates that the SLC22A9 variant F426S is causing inter-individual variation that is leading to the differences in transport of the steroid sulfate conjugate (estrone sulfate) and, therefore this could be used as a marker for certain disease including osteoporosis.