• 제목/요약/키워드: meta-pathway

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Folate Pathway Gene MTHFR C677T Polymorphism and Risk of Lung Cancer in Asian Populations

  • Rai, Vandana
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권21호
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    • pp.9259-9264
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    • 2014
  • Background: Previous studies concerning the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism with lung cancer in Asian populations have provided inconclusive findings. Aim: A meta-analysis was performed to investigate a more reliable association between MTHFR C677T polymorphism and lung cancer in Asians. Materials and Methods: A comprehensive search was conducted to identify all case-control studies of MTHFR polymorphisms and lung cancer in Asia, using odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. Results: Meta-analysis results suggested that the MTHFR C677T polymorphism contributed to an increased lung cancer risk in Asian populations (for T vs C: OR=1.11, 95%CI=1.0-1.23; for CT vs CC: OR= 1.1, 95%CI= 0.95-1.2 ; for TT+CT vs CC: OR=1.13, 95%CI=1.0-1.30; for TT vs CC: OR=1.25, 95%CI=1.01-1.30; for TT vs CT+CC: OR=1.16, 95%CI=1.0-1.36). Conclusions: MTHFR C677T polymorphism is significantly associated with lung cancer in Asians.

Association between the XRCC3 Thr241Met Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis

  • Sahami-Fard, Mohammad Hossein;Mayali, Ali Reza Mousa;Tajehmiri, Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권10호
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    • pp.4599-4608
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    • 2016
  • Background: The x-ray repair cross-complementing group 3 (XRCC3) encodes a protein involved in the homologous recombination repair (HRR) pathway for double-strand DNA repair. Associations of the XRCC3 Thr241Met polymorphism with various cancers have been widely reported. However, published data on links between XRCC3 Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. Objective and Methods: A meta-analysis was conducted to characterize the relationship between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooled odds ratios (ORs) and 95.0% confidence intervals were assessed using random- or fixed- effect models for 28.0 relevant articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls. Results: The results of the overall meta-analysis suggested a borderline association between the XRCC3 Thr241Met polymorphism and GI cancer susceptibility (T vs. C: OR=1.18, 9 % CI=1.0-1.4, POR=0.04; TT vs. CT+CC: OR=1.3, 95 % CI=1.0-1.6, POR=0.04). After removing studies not conforming to Hardy-Weinberg equilibrium (HWE), however, this association disappeared (T vs. C: OR=1.00, 95 % CI=0.9-1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8-1.1, POR=0.72). When stratified by ethnicity, source of controls or cancer type, although some associations between XRCC3 Thr241Met polymorphism and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming to HWE. Conclusion: Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with risk of GI cancer based on current evidence.

Association of Functional Polymorphisms of the XRCC4 Gene with the Risk of Breast Cancer: A Meta-analysis

  • Zhou, Li-Ping;Luan, Hong;Dong, Xi-Hua;Jin, Guo-Jiang;Ma, Dong-Liang;Shang, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권7호
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    • pp.3431-3436
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    • 2012
  • Objective: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks (DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of the XRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusive results. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and the risk of breast cancer. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searched for all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons of the total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases and controls. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. Results: Five studies were included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showed that mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increased risk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer. However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms of XRCC4 gene did not appear to have an influence on breast cancer susceptibility. Conclusion: Results from the current meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 gene might increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protective factors.

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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    • 제12권4호
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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.

Two Different Pathways (a Chlorocatechol and a Hydroquinone Pathway) for the 4-Chlorophenol Degradation in Two Isolated Bacterial Strains

  • Bae, Hee-Sung;Rhee, Sung-Keun;Cho, Young-Gyun;Hong, Jong-Ki;Lee, Sung-Taik
    • Journal of Microbiology and Biotechnology
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    • 제7권4호
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    • pp.237-241
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    • 1997
  • Two isolated strains, Comamonas testosteroni CPW301 and Arthrobacter ureafaciens CPR706, were able to use 4-chlorophenol (4-CP) as a sole carbon and energy source. CPW301 was found to degrade 4-CP via a meta-cleavage pathway in which the chloro-substituent was eliminated even when 4-chlorocatechol was cleaved by the catechol 2, 3-dioxygenase. In contrast, CPR706 removed chloride from 4-CP prior to the ring-fission reaction, producing hydroquinone as a transient intermediate during 4-CP degradation. CPR706 exhibited much higher tolerance for 4-CP than CPW301, which was indicated by the maximum degradable concentration and degradation rate.

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Kinetic and Theoretical Consideration of 3,4- and 3,5-Dimethoxybenzoyl Chlorides Solvolyses

  • Park, Kyoung-Ho;Kevill, Dennis N.
    • Bulletin of the Korean Chemical Society
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    • 제34권10호
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    • pp.2989-2994
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    • 2013
  • The solvolysis rate constants of 3,4- (1) and 3,5-dimethoxybenzoyl (2) chlorides were measured in various pure and binary solvents at $25.0^{\circ}C$, and studied by application of the extended Grunwald-Winstein (G-W) equation, kinetic solvent isotope effect in methanolysis and activation parameters. The solvolysis of 1 was interpreted as the unimolecular pathway due to a predominant resonance effect from para-methoxy substituent like 4-methoxybenzoyl chloride (3), while that of 2 was evaluated as the dual mechanism, with unimolecular or bimolecular reaction pathway according to the character of solvent systems (high electrophilic/nucleophilic) chosen, caused by the inductive effect by two meta-methoxy substituents, no resonance one. In the solvolyses of 1 and 2 with two $-OCH_3$ groups, the resonance effect of para-methoxy substituent is more important to decide the mechanism than the inductive effect with other corresponding evidences.

Characterization of 2-hydroxymuconic semialdehyde dehydrogenase from Burkholderia cepacia G4

  • A. Matta Reddy;Min, Kyung-Rak;Kim, Young-Soo
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.218.2-219
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    • 2003
  • 2-Hydroxymuconic semialdehyde dehydrogenase catalyzes the conversion of 2-hydroxymuconic semialdehyde (HMS) to an enol form of 4-oxalocrotonate which is a step in the catechol-meta cleavage pathway. A tomC gene encoding 2-HMS dehydrogenase of Burkholderia cepacia G4, a soil bacterium that can grow on toluene, cresol, phenol or tricholoro ethylene, is identified in between catechol 2,3-dioxygenase gene and HMS hydrolase gene, its sequence is analysed and the enzyme is characterised. (omitted)

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Aniline 분해균주 Burkholderia sp. HY1과 Delftia sp. HY99에서 유래된 Aniline Dioxygenases 유전자의 비교 분석 (Comparative Analysis of Aniline Dioxygenase Genes from Aniline Degrading Bacteria, Burkholderia sp. HY1 and Delftia sp. HY99.)

  • 강형일;오계헌
    • 한국미생물·생명공학회지
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    • 제35권2호
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    • pp.104-111
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    • 2007
  • 본 연구에서는 단일 탄소원과 질소원으로 aniline을 이용하는 것으로 보고된 바 있는 Bukholderia sp. HY1과 Deiftia sp. HY99로부터 aniline의 첫 번째 분해 단계에 관련된 aniline dioxygenas의 위치를 확인하고 그 유전자를 클로닝하여 아미노산 서열을 결정하고 비교하였다. 한 개 이상의 플라스미드 DNA를 포함하고 있을 것으로 조사된 B.a sp. HY1에서 유래된 플라스미드의 curing 실험을 통해, B. sp. HY1의 aniline oxygenase는 플라스미드가 아닌 염색체 DNA에 존재하는 것으로 확인되었다. B. sp. HY1과 D. sp. HY99에서 유래된 aniline dioxygenase small subunit는 146개 아미노산을 기준으로 약 79%의 상동성을 보였다. 특히, B. sp. HY1으로부터 얻어진 ado2는 aniline dioxygenase small subunit의 terminal dioxygenase에 속하는 것으로 Frateuria sp. ANA-18의 tdnA2와 99%, 그리고 Delftia sp. HY99의 ado2는 Delftia sp. AN3의 danA2와 99% 이상의 아미노산 상동성을 나타내었다. 또한 본 연구에서 두 균주에서 얻어진 catechol oxygenase의 아미노산 서열분석을 통해 B. sp. HY1은 catechol 1,2-dioxygenase에 의해 ortho pathway를 D. sp. HY99는 catechol 2,3-dioxygenase에 의해 meta pathway를 운영할 것이라는 이전 보고를 강력하게 뒷받침해 주었다.

TOL 플라스미드 세균의 분리와 특성 (Isolation and Characterization of Naturally Occuring Bacteria Carried TOL Plasmid)

  • Nam, Cho-Byung;Cho, In-Sun;Rhee, Young-Ha;Ryu, Jae-Keun;Min, Kyung-Hee
    • 한국미생물·생명공학회지
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    • 제17권4호
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    • pp.321-326
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    • 1989
  • m-Toluate 최소배지에서 선택적 enrichment culture를 통하여 82개의 세균의 균주를 분리하였으며, ol들 중 두 균주는 Pseudomonas cepacia, 한 균주는 P. Putida, 한 균주는 Yersinia intermedia, 그리고 한 균주는 Flavobacterium odoratum으로 동정되었다. P. cepacia SUB37은 P. putida mt-2의 TOL 플라스미드와 비슷한 크기의 플라스미드를 가지고 있었으며, Flavobacterium odoratum과 Yersinia intermedia는 이보다 더 큰 플라스미드를 갖고 있었다. P. cepacia SUB37은 streptomycin에 감수성을 나타내었으나, rifampicin에는 내성을 나타내었다. 플라스미드를 갖는 P. cepacia SUB37은 탄화수소를 해당 알콜과 알데히드를 거쳐서 benzoate와 toluate 로 분해하였다. 플라스미드 제거실험으로, P. Cepacia SUB37의 플라스미드에는 탄화수소 분해과정 중 toluene과 xylene을 benzoate, toluate로 분해하는 효소와, 계속하여 meta pathway를 거치는 단계의 효소를 코딩하는 유전자들이 있음이 확인되었다. 또한 P. cepacia SUB37은 생장이 왕성하였을 때 m-toluate를 거의 분해하였다.

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DFT/B3LYP Study of the Substituent Effects on the Reaction Enthalpies of the Antioxidant Mechanisms of Magnolol Derivatives in the Gas-Phase and Water

  • Najafi, Meysam;Najafi, Mohammad;Najafi, Houshang
    • Bulletin of the Korean Chemical Society
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    • 제33권11호
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    • pp.3607-3617
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    • 2012
  • In this paper, the study of various ortho- and meta-substituted Magnolol derivatives is presented. The reaction enthalpies related to three antioxidant action mechanisms HAT, SET-PT and SPLET for substituted Magnolols have been calculated using DFT/B3LYP method in gas-phase and water. Calculated results show that electron-withdrawing substituents increase the bond dissociation enthalpy (BDE), ionization potential (IP) and oxidation/reduction enthalpy (O/RE), while electron-donating ones cause a rise in the proton dissociation enthalpy (PDE) and proton affinity (PA). In ortho- position, substituents show larger effect on reaction enthalpies than in meta-position. In comparison to gas-phase, water attenuates the substituent effect on all reaction enthalpies. In gas-phase, BDEs are lower than PAs and IPs, i.e. HAT represents the thermodynamically preferred pathway. On the other hand, SPLET mechanism represents the thermodynamically favored process in water. Results show that calculated enthalpies can be successfully correlated with Hammett constants (${\sigma}_m$) of the substituted Magnolols. Furthermore, calculated IP and PA values for substituted Magnolols show linear dependence on the energy of the highest occupied molecular orbital ($E_{HOMO}$).