• Title/Summary/Keyword: ace gene

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Angiotensin-converting Enzyme Gene Polymorphism and Cerebrovascular Disease in Korean population (한국인의 ACE(Angiotensin-converting Enzyme) 유전자의 다형성과 뇌혈관 질환과의 관계에 대한 연구)

  • Lee Jin Woo;Lee Kyung Jin;Rho Sam Woong;Kim Jae Jong;Bae Hyung Sup;Hong Moo Chang;Shin Min Kyu;Kim Young Suk;Bae Hyun Su
    • 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.

Gene-gene interaction in cerebral infarction patients: Relationship between apolipopreotein E gene polymorphism and Sasang-constitution

  • Um, Jae-Young;Kim, Jong-Kwan;Joo, Jong-Cheon;Kim, Kyung-Yo;Hong, Seung-Heon;Kim, Hyung-Min
    • Advances in Traditional Medicine
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    • v.4 no.2
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    • pp.104-111
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    • 2004
  • Sasang Constitutional Medicine is a major branch of Korean Traditional Oriental Medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction (CI), apolipoprotein E (apoE) gene polymorphism, and Sasang constitutional classification. ApoE is a key protein modulating the highly atherogenic apoB containing lipoproteins and is a candidate gene for the development of coronary artery disease (CAD). The ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles were the first to be implicated in premature CAD, which resulted in this polymorphism being extensively studied. We investigated the association between apoE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang Constitutional Medicine. 196 CI patients and 379 controls without CI were examined. ApoE genotype was determined by 8% polyacrylamide gel separation after DNA amplification. A significant difference in the apoE genotype distribution was observed in the CI patients compared with that in controls ($X^{2}$=14.920, df=4, P=0.005). Also, the frequency of Taeumin constitution in patients with CI was significantly higher than that in controls (58.0% vs. 36.9%; P<0.001). However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with apoE ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles. No differences in the apoE genotypes frequencies were observed in the Taeumin compared with that in the other constitutions. In addition, we investigated whether the DD genotype of angiotensin converting enzyme (ACE) gene, a candidate gene for CI, was associated with CI, Taeumin constitution, and apoE polymorphism. As a result, the frequency of Taeumin constitution was significantly higher in CI patients with both apoE ${\varepsilon}3/{\varepsilon}4$ and ACE ID/DD genotypes than in the remaining Sasang constitutions (14.5% vs. 8.3% and 0%) ($X^{2}$=13.521, df=6, P=0.035). In summary, we concluded that the apoE polymorphism is a major risk factor for CI in Koreans and the ACE ID/DD genotype enhanced the relative risk for CI in the subjects with apoE ${\varepsilon}3/{\varepsilon}4$ genotype and Taeumin constitution.

Expression and Purification of an ACE-Inhibitory Peptide Multimer from Synthetic DNA in Escherichia coli

  • OH, KWANG-SEOK;YONG-SUNG PARK;HA-CHIN SUNG
    • Journal of Microbiology and Biotechnology
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    • v.12 no.1
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    • pp.59-64
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    • 2002
  • An angiotensin I-converting enzyme (EC 3.4.15.1) (ACE), which can convert inactive angiotensin I into angiotensin II, a vasoconstrictor, is one of the key enzymes in controlling hypertension. It is suggested that the inhibition of ACE prevents hypertension, and many inhibitory peptides have already been reported. In the current study, oligonucleotides encoding ACE inhibitory peptides (IY, VKY) were chemically synthesized and designed to be multimerised due to isoschizomer sites (BamHI, BglII). The cloned gene named AP3 was multimerised up to 6 times in pBluescript and expressed in BL2l containing pGEX-KG. The fusion protein (GST-AP3) was easily purified with a high recovery by an affinity resin, yielding 38 mg of synthetic AP3 from a 1-1 culture. The digestion of AP3 by chymotrypsin exhibited an $IC_50$ value of $18.53{\mu}M$. In conclusion, the present experiment indicated that AP3 could be used as a dietary antihypertensive drug, since the potent ACE inhibitory activity of AP3 could be activated by chymotrypsin in human intestine.

Association between the Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism and Essential Hypertension in Young Pakistani Patients

  • Ismail, Muhammad;Akhtar, Naveed;Nasir, Muhammad;Firasat, Sadaf;Ayub, Qasim;Khaliq, Shagufta
    • BMB Reports
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    • v.37 no.5
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    • pp.552-555
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    • 2004
  • Several studies have demonstrated the importance of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms in the pathogenesis of hypertension. This study sought to determine the association between the ACE I/D polymorphism and essential hypertension in young Pakistanis. The frequency of the ACE I/D polymorphism was established by a comparative cross-sectional survey of Pakistani patients suffering from essential hypertension and ethnically matched normotensive controls. Samples were collected from tertiary care hospitals in northern Pakistan. Hypertensive individuals were defined as those with a systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg on three separate occasions, or those currently receiving one, or more, anti-hypertensive agents. DNA samples obtained from hypertensive (n=211) and normotensive (n=108) individuals were typed by PCR. The frequency of the ACE I/I genotype was significantly higher in hypertensive patients, aged 20-40 years, than in normotensive controls of the same age group ($\chi^2$ = 4.0, P = 0.041). Whereas no overall significant differences were observed between the I/I, I/D and D/D ACE genotypes (One way ANOVA, F=0.672; P=0.413). The association between the ACE I/I genotype and essential hypertension in individuals aged $\leq$ 40 years suggests that ACE has a role in early onset essential hypertension in Pakistan.

Isolation and Characterization of Lactic Acid Bacteria with Angiotensin-Converting Enzyme Inhibitory and Antioxidative Activities (안지오텐신 전환효소 저해 활성 및 항산화 활성을 가진 젖산균의 분리 및 특성)

  • Park, Sung-Bo;Kim, Jeong-Do;Lee, Na-Ri;Jeong, Jin-Ha;Jeong, Seong-Yun;Lee, Hee-Seob;Hwang, Dae-Youn;Lee, Jong-Sup;Son, Hong-Joo
    • Journal of Life Science
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    • v.21 no.10
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    • pp.1428-1433
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    • 2011
  • In this study, we isolated and characterized plant-associated lactic acid bacteria which are able to produce angiotensin-converting enzyme (ACE) inhibitory and antioxidative activities. Five lactic acid bacteria were isolated from plants (grape and leek), a plant-associated fermentative product (Kimchi) and Korean traditional alcohol (Dongdongju). Strains K-1 and K-21 from Kimchi, strain L-5 from leek, strain G-3 from grape, and strain D-3 from Dongdongju were identified as Pediococcus pentosaceus, Lactobacillus plantarum, Weissella cibaria, L. plantarum, and L. brevis, respectively, by 16S rRNA gene analysis. ACE inhibitory activities of isolated strains ranged from 44.3 to 71.9% in the MRS broth. G-3, L-5 and K-1 strains especially showed high ACE inhibitory activities (59.8-98.69%) in the MRS broth containing skim milk. DPPH radical scavenging activities of the strains were in the range of 42.5-82.7%. All strains showed varying levels of resistance in artificial gastric fluid (pH 2.5), retaining viability ranging from 42.2 to 88.1% after 3 hr of incubation. All strains showed high resistance to 0.3% oxgall after 24 hr of incubation; survival rates were in the range of 55.4-112.8%. Isolated strains were found to be antagonistic to some pathogens including Pseudomonas aeruginosa.

Change of Gene Expression Pattern of Mycobacterium tuberculosis H37Rv Against Host Immune Response in Infected Mouse Lung (결핵균 H37Rv에 감염된 마우스의 폐에서 면역 반응에 대항하는 Mtb 유전자의 발현 변화)

  • Lee, Hyo-Ji;Cho, Jung-Hyun;Kang, Su-Jin;Jung, Yu-Jin
    • Korean Journal of Microbiology
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    • v.46 no.2
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    • pp.134-139
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    • 2010
  • Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens to infect one third of world population. Th1-mediated immunity against Mtb infection is known as critical to express mycobacteriostatic function but it is not sufficient to resolve the infection. In this study, to verify the possibility Mtb itself change the gene expression to survive against host immune response, expression pattern of selected H37Rv genes, 16S rRNA, acr, fbpA, aceA, and ahpC, during the course of infection was measured with absolute quantitation method using real-time RT-PCR. The total number of transcripts of 16S rRNA increased during the course of infection, which was coincide with the increasing CFU. The total number of fbpA transcripts per CFU, which encode typical secreted Mtb antigen, Ag85A, increased for 10 days of infection before decreasing. The number of transcripts of acr per CFU, which encode heat shock protein, ${\alpha}$-crystallin, increased during the infection, and ahpC and aceA, they both are enzymes produced in oxidative stressful condition, increased for 20 days and then slightly decreased on day 30. These findings are one of survival strategy of pathogen evading host immune response lead to persistent infection inside host cells.

Site-specific Disruption of Glyoxylate Bypass and Its Effect in Lysine-producing Corynebacterium lactofermentum Strain

  • Kim, Youn-Hee;Lee, Heung-Shick
    • Journal of Microbiology and Biotechnology
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    • v.6 no.5
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    • pp.315-320
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    • 1996
  • The role of glyoxylate bypass in a lysine-producing Corynebacterium lactofermentum strain was analyzed. Unlike the wild type, the strain expressed enzymes of glyoxylate bypass during growth in the fermentation broth containing glucose as the carbon source. To evaluate the importance of glyoxylate bypass in the strain, we disrupted chromosomal aceA by using a cloned fragment of the gene. Site-specific disruption of aceA which codes for the isocitrate lyase, the first enzyme of the bypass, was confirmed by Southern blot analysis. The aceA mutant strain completely lost isocitrate lyase activity and ability to grow in a minimal medium containing acetate as the sole carbon source. The mutant strain was similar to its parental strain in growth characteristics and produced comparable amounts of lysine in shake flasks containing glucose as the carbon source. The amount of oxaloacetate accumulated in the fermentation medium was similar for both strains, suggesting that expression of glyoxylate bypass does not necessarily lead to the increase in intracellular oxaloacetate. These data clearly demonstrate that glyoxylate bypass does not function as one of the routes of carbon supply for lysine production in the strain. It appears that the leakiness of the glyoxylate bypass in the strain might be the result of a secondary mutation which arose during previous strain development by random mutagenesis.

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Utilization of lacZ to Isolate Regulatory Genes from Corynebacterium glutamicum

  • KIM, HYUNG-JOON;JOON-SUNG PARK;HEUNG-SHICK LEE;YOUNHEE KIM
    • Journal of Microbiology and Biotechnology
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    • v.12 no.2
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    • pp.336-339
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    • 2002
  • A total of 100 Corynebacterial clones exerting a regulatory effect on the aceB promoter of Corynebacterium glutamicum were isolated by utilizing a reporter carrying the enteric lacZ gene fused to the promoter. The isolated clones were classified into 3 groups of A, B, and C, according to their color of colonies. Escherichia coli cells carrying clones in groups A and B showed a $90\%\;and\;50\%$ reduction in ${\beta}$-galactosidase activity, respectively. The introduction of group A clones into C. glutamicum also resulted in an almost complete reduction in the expression of the aceA and aceB genes, suggesting that the clones express repressor-like proteins for the genes. Although white colonies were formed on plates containing X-gal, E. coli cells carrying one of the clones in group C exhibited intact ${\beta}$-galactosidase activity. The result suggests that the clone may encode proteins that prevent the cells from accumulating the chromogenic compound, X-gal.

Antimicrobial and ACE Inhibitory Activities of Citrus unshiu Fermented with Lactic Acid Bacteria (감귤 유산균 발효물의 항균 활성과 ACE 저해능)

  • Choi, So-Yeon;Kim, Si-Kyung;Youn, Un-Young;Kang, Dae-Ook;Choi, Nack-Shick;Mun, Mi-Sun;Lee, Seung-Cheol
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.7
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    • pp.1084-1089
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    • 2015
  • To develop high quality citrus products, seven lactic acid bacteria were innoculated onto ground citrus (Citrus unshiu) and cultured for 10 days. On culture days 0, 3, 5, 7, and 10, citrus ferments were withdrawn, and their antimicrobial and angiotensin-I converting enzyme (ACE) inhibitory activities were evaluated. Citrus ferments innoculated with CL-1 and CL-2, which were isolated from kimchi, showed relatively higher antimicrobial activities against food poisoning bacteria. Citrus ferments innoculated with CL-1 and CL-2 also showed stronger ACE inhibitory activities than other ferments. CL-1 and CL-2 showed more than 99% homogeny with Pediococcus acidilactici and Lactobacillus sakei, respectively, by 16S rRNA gene analysis. These results indicate that fermentation with P. acidilactici and L. sakei might contribute to the increased antimicrobial and anti-hypertensive activities of citrus.

Haplotype-Based Association and Linkage Analysis of Angiotensin-I Converting Enzyme(ACE) Gene with a Hypertension (일배체형에 기초한 고혈압과 ACE 유전자의 연관성 분석)

  • Kim Jinheum;Nam Chung Mo;Kang Dae Ryong;Suh Il
    • The Korean Journal of Applied Statistics
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    • v.18 no.2
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    • pp.297-310
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    • 2005
  • In this study we investigate the association between the haplotype block of 4 SNPs in ACE genes and hypertension with a case-control dataset of size of 277 and 40 families data collected from Kangwha studies. To this end we perform a haplotype-based case-control association study and a haplotype-based TDT study. We do the same analysis with tag-SNPs that can identify the haplotype block. Through a cladogram analysis we make the evolution-tree of haplotypes and then classify the haplotypes into a few clades by collecting haplotypes exposed to the disease to the same extent. We also discuss the association between these clades and hypertension.