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Polymorphisms in DNA Repair Genes and <i>MDR1</i> and the Risk for Non-Hodgkin Lymphoma
Kim, Hee Nam,Kim, Nan Young,Yu, Li,Kim, Yeo-Kyeoung,Lee, Il-Kwon,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min-Ho,Park, Kyeong-Soo,Choi, Jin-Su,Kim, Hyeoung-Joon Molecular Diversity Preservation International (MD 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.4
<P>The damage caused by oxidative stress and exposure to cigarette smoke and alcohol necessitate DNA damage repair and transport by multidrug resistance-1 (MDR1). To explore the association between polymorphisms in these genes and non-Hodgkin lymphoma risk, we analyzed 15 polymorphisms of 12 genes in a population-based study in Korea (694 cases and 1700 controls). Four genotypes of DNA repair pathway genes (<I>XRCC1</I> 399 GA, <I>OGG1</I> 326 GG, <I>BRCA1</I> 871 TT, and <I>WRN</I> 787 TT) were associated with a decreased risk for NHL [odds ratio (<I>OR</I>)<SUB>XRCC1 GA</SUB> = 0.80, <I>p</I> = 0.02; <I>OR</I><SUB>OGG1 GG</SUB> = 0.70, <I>p</I> = 0.008; <I>OR</I><SUB>BRCA1 TT</SUB> = 0.71, <I>p</I> = 0.048; <I>OR</I><SUB>WRN TT</SUB> = 0.68, <I>p</I> = 0.01]. Conversely, the <I>MGMT</I> 115 CT genotype was associated with an increased risk for NHL (<I>OR</I> = 1.25, <I>p</I> = 0.04). In the <I>MDR1</I> gene, the 1236 CC genotype was associated with a decreased risk for NHL (<I>OR</I> = 0.74, <I>p</I> = 0.04), and the 3435 CT and TT genotypes were associated with an increased risk (<I>OR</I><SUB>3435CT</SUB> = 1.50, <I>p</I> < 0.0001; <I>OR</I><SUB>3435TT</SUB> = 1.43, <I>p</I> = 0.02). These results suggest that polymorphisms in the DNA repair genes <I>XRCC1</I>, <I>OGG1</I>, <I>BRCA1</I>, <I>WRN1</I>, and <I>MGMT</I> and in the <I>MDR1</I> gene may affect the risk for NHL in Korean patients.</P>
Molecular Authentication of Acanthopanacis Cortex by Multiplex-PCR Analysis Tools
Kim, Min-Kyeoung,Jang, Gyu-Hwan,Yang, Deok-Chun,Lee, Sanghun,Lee, Hee-Nyeong,Jin, Chi-Gyu The Plant Resources Society of Korea 2014 한국자원식물학회지 Vol.27 No.6
Acanthopanacis Cortex has been used for oriental medicinal purposes in Asian countries especially in Korea and China. In the Korean Pharmacopeia, the cortexes of the dried roots, stems and branches of all species in Eleutherococcus and Eleutherococcus sessiliflorus are known as 'Ogapi'. Mostly the cortexes of E. gracilistylus roots and E.senticosus roots were used as 'Ogapi' in China and Japan, respectively. Therefore, the purpose of this study was to determine and compare the molecular authentication of Korean 'Ogapi' by using the ribosomal internal transcribed spacer (ITS) region. The ITS region has the highest possibility of effective and successful identification for the widest variety of molecular authentication. The ITS region was targeted for molecular analysis with Single nucleotide polymorphisms (SNPs) specific for morphologically similar to E. gracilistylus, E. senticosus, E. sessiliflorus from their adulterant, moreover, E. sieboldianus were detected within sequence data. Thus, based on these SNP sites, specific primers were designed and multiplex PCR analysis were conducted for molecular authentication of four plants (E. gracilistylus, E. senticosus, E. sessiliflorus, and E. sieboldianus). The findings of results indicated that ITS region might be established multiplex-PCR analysis systems and hence were proved to be an effective tools for molecular evaluation and comparison of 'Ogapi' with other plants.
Kim, Hyoun Sook,Kim, Jieun,Im, Ha Na,Yoon, Ji Young,An, Doo Ri,Yoon, Hye Jin,Kim, Jin Young,Min, Hye Kyeoung,Kim, Soon-Jong,Lee, Jae Young,Han, Byung Woo,Suh, Se Won International Union of Crystallography 2013 Acta crystallographica. Section D, Biological crys Vol.69 No.3
<▼1><P>The crystal structure of <I>M. tuberculosis</I><SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidase (Ldt<SUB>Mt2</SUB>; Rv2518c) has been determined in both ligand-free and meropenem-bound forms. The detailed view of the interactions between meropenem and Ldt<SUB>Mt2</SUB> will be useful in structure-guided discovery of new antituberculosis drugs.</P></▼1><▼2><P>Difficulty in the treatment of tuberculosis and growing drug resistance in <I>Mycobacterium tuberculosis</I> (<I>Mtb</I>) are a global health issue. Carbapenems inactivate <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidases; meropenem, when administered with clavulanate, showed <I>in vivo</I> activity against extensively drug-resistant <I>Mtb</I> strains. Ldt<SUB>Mt2</SUB> (Rv2518c), one of two functional <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidases in <I>Mtb</I>, is predominantly expressed over Ldt<SUB>Mt1</SUB> (Rv0116c). Here, the crystal structure of N-terminally truncated Ldt<SUB>Mt2</SUB> (residues Leu131–Ala408) is reported in both ligand-free and meropenem-bound forms. The structure of meropenem-inhibited Ldt<SUB>Mt2</SUB> provides a detailed structural view of the interactions between a carbapenem drug and <I>Mtb</I><SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidase. The structures revealed that the catalytic <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidase domain of Ldt<SUB>Mt2</SUB> is preceded by a bacterial immunogloblin-like Big_5 domain and is followed by an extended C-terminal tail that interacts with both domains. Furthermore, it is shown using mass analyses that meropenem acts as a suicide inhibitor of Ldt<SUB>Mt2</SUB>. Upon acylation of the catalytic Cys354 by meropenem, the ‘active-site lid’ undergoes a large conformational change to partially cover the active site so that the bound meropenem is accessible to the bulk solvent <I>via</I> three narrow paths. This work will facilitate structure-guided discovery of <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidase inhibitors as novel antituberculosis drugs against drug-resistant <I>Mtb</I>.</P></▼2>
Polymorphisms of drug-metabolizing genes and risk of non-Hodgkin lymphoma
Kim, Hee Nam,Kim, Nan Young,Yu, Li,Kim, Yeo-Kyeoung,Lee, Il-Kwon,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min-Ho,Park, Kyeong-Soo,Choi, Jin-Su,Kim, Hyeoung-Joon Wiley Subscription Services, Inc., A Wiley Company 2009 American journal of hematology Vol.84 No.12
<P>Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug-metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non-Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population-based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)<SUB>AG</SUB> = 0.67, 95% confidence interval (CI) = 0.55–0.82; OR<SUB>AG/GG</SUB> = 0.66, 95% CI = 0.54–0.80) and DLBCL (OR<SUB>AG</SUB> = 0.63, 95% CI = 0.49–0.82; OR<SUB>AG/GG</SUB> = 0.64, 95% CI = 0.50–0.82). For T-cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (OR<SUB>AG/GG</SUB> = 0.65, 95% CI = 0.44–0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (OR<SUB>AG</SUB> = 1.28, 95% CI = 1.07–1.54; OR<SUB>AG/GG</SUB> = 1.26, 95% CI = 1.06–1.51) and DLBCL (OR<SUB>AG</SUB> = 1.32, 95% CI = 1.04–1.66; OR<SUB>AG/GG</SUB> = 1.30, 95% CI = 1.03–1.63), but not T-cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc.</P>