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Shin, Dong-Jik,Kim, Jongmin,Bae, Yoonjung,Kim, Eunmin,Kim, Jeong Ki,Rhim, Hyangshuk,Park, Chanmi,Park, Hyun-Young,Jang, Yangsoo,Lee, Jong-Eun,Kim, Wook,Kim Yoon, Sungjoo 한국유전학회 2004 Genes & Genomics Vol.26 No.4
The genes encoding α-adducin (ADD1, G460W polymorphism) and angiotensin I-converting enzyme (ACE, T2547C and I/D polymorphisms) have been implicated in essential hypertension (EH) and may regulate the blood pressure (BP) regulation through sodium homeostasis. In order to investigate whether the polymorphisms in these genes are associated with EH in Koreans, we carried out a case-control study of 449 hypertensive cases and age-/gender-matched 459 normotensive controls recruited from Cardiovascular Genome Center of Yonsei University in Korea. The genotypes for these polymorphisms were determined by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and the allelic-specific PCR for I/D, T2547C, and G460W, respectively. The genotype frequency of ACE T2547C polymorphism was significantly different between the hypertensive and the normotensive subjects, which was only present in females (P = 0.019). ACE 2547C homozygosity, in comparison with the other ACE genotypes, was strongly associated with increase in the incidence of hypertension (OR, 1.788; 95% CI, 1.139-2.809, P = 0.011) in single-gene analyses. The pairwise linkage disequilibrium (LD) test was found to be in significant LD (D´ = 0.958) between ACE T2547C and I/D polymorphisms in our study population. In haplotype and logistic regression analyses, significant OR was also observed for ACE haplotype CD within the ADD1 460 T carriers in the female group (OR, 1.334; 95% CI, 1.004-1.772, P = 0.047). Interestingly in males, the group with ACE haplotype CD had significantly low incidence of hypertension in the presence of the ADD1 460 TT homozygosity in males (OR, 0.530; 95% CI, 0.328-0.859, P = 0.010). These findings suggest that the ACE gene polymorphisms may be associated with some determinants increasing BP, and imply an interaction between ACE and ADD1 gene polymorphisms is a positive genetic risk factor for EH in females.
Genetic Association of the ACE Gene Polymorphisms with Essential Hypertension in Korean Females
( Dong Jik Shin ),( Yoon Sun Bae ),( Ji Hye Han ),( Chan Mi Park ),( Sung Ha Park ),( Hyun Joon Shin ),( Young Guk Ko ),( Dong Hoon Choi ),( Ki Chul Hwang ),( Ji Hyung Chung ),( Sung Joo Kim ),( Yang 한국조직공학과 재생의학회 2006 조직공학과 재생의학 Vol.3 No.3
The renin-angiotensin system(RAS) genes have been extensively studied as etiologic essential hypertension( EH) candidate genes in human populations worldwide. The angiotensin I-converting enzyme(ACE) plays a key role in the RAS for the regulation of blood pressure. Recent studies on the association of ACE gene polymorphisms with EH and the related cardiovascular diseases presented conflicting results. Therefore, we investigated the association of three polymorphisms(I/D, G14480C and A22982G) in the ACE gene with EH in Koreans. We studied a sample population of 699 Koreans, comprising of 471 controls and 228 cases with EH, which were recruited from Cardiovascular Genome Center in Korea. The ACE gene polymorphisms were determined by polymerase chain reaction and SNP-IT assay. The allele frequency of G14480C polymorphism showed significant difference between normotensives and hypertensives in female group(P=0.0353). After adjustment for age and BMI, logistic regression analysis indicated that the odds ratio(OR) of the ACE I carriers(II+ID) for a risk of EH over the DD genotype was 1.698(95% CI, 1.006-2.864, P=0.0458), and OR for the comparison of 14480 GG subjects versus GC and CC subjects combined was for EH 1.787(95% CI, 1.076-2.967, P=0.0236) in females. In haplotype analysis, major three haplotypes(ICA, IGG, and DGG) were significantly associated with EH in study populations. We conclude that ACE polymorphisms appeared to have apparent association with EH in Koreans, who have a more homogeneous genetic structure than any other ethnic groups.
서울 서남부지역 노인인구에서 공복혈당 및 경구 당부하검사(ADA 및 WHO 당뇨병진단기준)에 의한 당뇨병의 유병률
김난희,최동섭,백세현,최경묵,신동현,박이병,김신곤,김동림,조영직,김경오 대한당뇨병학회 2001 Diabetes and Metabolism Journal Vol.25 No.2
Background: The prevalence of diabetes in Korea is increasing rapidly, however we do not have much reliable data to prove it. Thus, the Southwest Seoul Study (SWS Study) designed to investigate the prevalence of diabetes (Clinical impact of new diagnostic criteria of ADA compare to the one of WHO), other metabolic diseases, and the proportion of diabetes related mortalities in the elderly Korean southwest Seoul population in prospectively. However, in this report we summarized the prevalence of diabetes only. Methods: Randomly selected 1,737 elderly subjects over 60 years who lived in southwest area of Seoul were recruited in this study. Subjects underwent 75 g OGTT, interviewed using the standardized questionnaire, and careful physical examinations during the evaluation. Biochemical data were collected from 1,652 subjects and were analysed for this report. Of 1,652 subjects, we identified 196 pre-diabetics. However, these subjects were included in this analysis. ADA criteria (FBS≥ 126 mg/dL (7.0 mmol/L)) and WHO criteria (75 gOGTT, pp2h≥ 200 mg/dL (11.1 mmol/L)) were used as the criteria for diagnosis of diabetes. ADA and WHO criteria for impaired glucose tolerance (IGT, WHO: FBS$lt;7.0 mmol/L, 7.8 mmol/L ≤ pp2h $lt; 11.1 mol/L), and impaired fasting glucose (IFG, ADA:6.1 mmol/L ≤ FBS $lt; 7.0 mmol/L, pp2h $lt; 7.8 mmol/L) were also used. Results: The prevalence of Diabetes mellitus was 20.5% (previous diagnosed 196 people (11.9%), newly diagnosed 142 people (8.6%); total 338 people). Among 142 newly diagnosed people, 50 people diagnosed by new ADA criteria and 129 people were diagnosed by WHO criteria, thirty seven people were diagnosed by the both criteria. The number of IGT and IFG were 337 (20.4%) and 85 (5.1%) people, respectively. Conclusion: The prevalence of diabetes in Korean elderly who lived in southwest area of Seoul was 20.4%. The prevalence of IGT and IFG were 20.4%, 5.1 %, respectively. Furthermore, this study suggest that using the ADA fasting criteria only for screening of diabetes might cause . under diagnose of diabetes in elderly Korean.
Shin, Sun-Mi,Kim, Hana,Joo, Yunhye,Lee, Sang-Jae,Lee, Yong-Jik,Lee, Sang Jun,Lee, Dong-Woo American Chemical Society 2014 Journal of agricultural and food chemistry Vol.62 No.50
<P>The <I>gadB</I> gene encoding glutamate decarboxylase (GAD) from <I>Lactobacillus plantarum</I> was cloned and expressed in <I>Escherichia coli</I>. The recombinant enzyme exhibited maximal activity at 40 °C and pH 5.0. The 3D model structure of <I>L. plantarum</I> GAD proposed that its C-terminal region (Ile454–Thr468) may play an important role in the pH dependence of catalysis. Accordingly, C-terminally truncated (Δ3 and Δ11 residues) mutants were generated and their enzyme activities compared with that of the wild-type enzyme at different pH values. Unlike the wild-type GAD, the mutants showed pronounced catalytic activity in a broad pH range of 4.0–8.0, suggesting that the C-terminal region is involved in the pH dependence of GAD activity. Therefore, this study may provide effective target regions for engineering pH dependence of GAD activity, thereby meeting industrial demands for the production of γ-aminobutyrate in a broad range of pH values.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2014/jafcau.2014.62.issue-50/jf504656h/production/images/medium/jf-2014-04656h_0007.gif'></P>
Shin, Sun-Mi,Choi, Jin Myung,di Luccio, Eric,Lee, Yong-Jik,Lee, Sang-Jae,Lee, Sang Jun,Lee, Sung Haeng,Lee, Dong-Woo Elsevier 2015 Archives of biochemistry and biophysics Vol.585 No.-
<P><B>Abstract</B></P> <P>UDP-galactose 4-epimerase (GalE) catalyzes the interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDP-Gal), which is a pivotal step in the Leloir pathway for <SMALL>D</SMALL>-galactose metabolism. Although GalE is widely distributed in prokaryotes and eukaryotes, little information is available regarding hyperthermophilic GalE. We overexpressed the TM0509 gene, encoding a putative GalE from <I>Thermotoga maritima</I> (TMGalE), in <I>Escherichia coli</I> and characterized the encoded protein. To further investigate the molecular basis of this enzyme's catalytic function, we determined the crystal structures of TMGalE and TMGalE bound to UDP-Glc at resolutions of 1.9 Å and 2.0 Å, respectively. The enzyme was determined to be a homodimer with a molecular mass of 70 kDa. The enzyme could reversibly catalyze the epimerization of UDP-GalNAc/UDP-GlcNAc as well as UDP-Gal/UDP-Glc at elevated temperatures, with an apparent optimal temperature and pH of 80 °C and 7.0, respectively. Our data showed that TM0509 is a UDP-galactosugar 4-epimerase involved in <SMALL>D</SMALL>-galactose metabolism; consequently, this study provides the first detailed characterization of a hyperthermophilic GalE. Moreover, the promiscuous substrate specificity of TMGalE, which is more similar to human GalE than <I>E. coli</I> GalE, supports the notion that TMGalE might exhibit the earliest form of sugar-epimerizing enzymes in the evolution of galactose metabolism.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TMGalE is an enzyme that catalyzes the epimerization of UDP-hexose. </LI> <LI> We determined the crystal structures of TMGalE in complex with NAD<SUP>+</SUP> and UDP-glucose. </LI> <LI> This study provides molecular basis for the substrate promiscuity of TMGalE. </LI> <LI> The crystal structure may provide structural guide-lines for protein evolution. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>