• Title/Summary/Keyword: Apolipoprotein E

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The Impact of Choline Acetyltransferase Polymorphism on the Expression of Mild Cognitive Impairment (Choline Acetyltransferase 유전자 다형성이 경도인지손상 발현에 미치는 영향)

  • Lee, Jung-Jae;Park, Joon-Hyuk;Lee, Seok-Bum;Huh, Yoon-Seok;Kim, Tae-Hui;Youn, Jong-Chul;Jhoo, Jin-Hyeong;Lee, Dong-Young;Park, Koung-Un;Kim, Ki-Woong
    • Korean Journal of Biological Psychiatry
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    • v.17 no.4
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    • pp.218-225
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    • 2010
  • Objectives : The potential association between choline acetyltransferase(CHAT) polymorphism and the risk of mild cognitive impairment(MCI) has not been investigated in Korea. We examined the main effect of CHAT polymorphism and its interaction with apolipoprotein E(APOE) polymorphism in the development of MCI in elderly Korean sample. Methods : We analyzed CHAT 2384G > A polymorphism and APOE polymorphism among 149 MCI subjects with MCI and 298 normal controls. We tested the association between MCI and CHAT A allele status using a logistic regression model. In addition, we employed generalized multifactor dimensionality reduction(GMDR) to investigate the interaction between CHAT and APOE with regard to the risk of MCI. Results : The CHAT A allele was associated with AD risk(OR = 1.59, 95% CI = 1.02-2.48, p = 0.042). No significant gene-gene interaction between CHAT and APOE was found in GMDR method(testing balanced accuracy = 0.540, p = 0.055). Conclusion : The CHAT A allele was associated with MCI risk in the Korean elderly. Its interaction with the APOE ${\varepsilon}4$ allele was not significant with regard to the development of MCI.

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.

Sulfasalazine attenuates tamoxifen-induced toxicity in human retinal pigment epithelial cells

  • Hwang, Narae;Chung, Su Wol
    • BMB Reports
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    • v.53 no.5
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    • pp.284-289
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    • 2020
  • Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

Development of Cerebral Amyloid Positivity Predicting Models Using Clinical Indicators (임상적 지표를 이용한 대뇌 아밀로이드 단백 축적 여부 예측모델 개발)

  • Chun, Young Jae;Joo, Soo Hyun
    • Korean Journal of Biological Psychiatry
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    • v.27 no.2
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    • pp.94-100
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    • 2020
  • Objectives Amyloid β positron emission tomography (Aβ PET) is widely used as a diagnostic tool in patients who have symptoms of cognitive impairment, however, this diagnostic examination is too expensive. Thus, predicting the positivity of Aβ PET before patients undergo the examination is essential. We aimed to analyze clinical predictors of patients who underwent Aβ PET retrospectively, and to develop a predicting model of Aβ PET positivity. Methods 468 patients who underwent Aβ PET with cognitive impairment were recruited and their clinical indicators were analyzed retrospectively. We specified the primary outcome as Aβ PET positivity, and included variables such as age, sex, body mass index, diastolic blood pressure, systolic blood pressure, education, dementia family history, Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating-Sum of Box (CDR-SB), hypertension (HTN), diabetes mellitus (DM) and presence of apolipoprotein E (ApoE) E4 as potential predictors. We developed three final models of amyloid positivity prediction for total subjects, mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia using a multivariate stepwise logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) value was calculated for the ROC curve. Results Aβ PET negative patients were 49.6% (n = 232), and Aβ PET positive patients were 50.4% (n = 236). In the final model of all subjects, older age, female sex, presence of ApoE E4 and lower MMSE are associated with Aβ PET positivity. The AUC value was 0.296. In the final model of MCI subjects (n = 244), older age and presence of ApoE E4 are associated with Aβ PET positivity. The AUC value was 0.725. In the final model of AD subjects (n = 173), lower MMSE scores, the presence of ApoE E4 and history of HTN are associated with Aβ PET positivity. The AUC value was 0.681. Conclusions The cerebral amyloid positivity model, which was based on commonly available clinical indicators, can be useful for prediction of amyloid PET positivity in MCI or AD patients.

Effects of Aerobic Exercise on Serum Blood Lipids, Leptin, Ghrelin, and HOMA-IR Factors in Postmenopausal Obese Women (유산소 운동이 폐경 후 비만여성의 혈청지질, 렙틴, 그렐린 및 인슐린저항성지수에 미치는 영향)

  • Lee, Jeong-Ah;Kim, Ji-Hyeon;Kim, Jong-Won;Kim, Do-Yoen
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.2
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    • pp.549-558
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    • 2017
  • The aim of this study was to analyze the effects of aerobic exercise on the blood lipids, leptin, ghrelin, and HOMA-IR factors in obese postmenopausal Korean women. Thirty-six healthy postmenopausal women (mean age, $54.47{\pm}2.50$ years) with >32 % body fat were assigned randomly to an aerobic exercise group (n = 18) or to a "no exercise" control group (n = 18). The subjects' body composition, blood lipid, leptin, ghrelin levels, and HOMA-IR were measured before and after a 16-week line-dancing program. The exercise group showed a significant decrease in body weight, percent body fat, body mass index, visceral fat area, leptin, insulin, glucose, HOMA-IR, total cholesterol, triglycerides, apolipoprotein B, low-density lipoprotein cholesterol, and systolic and diastolic blood pressure. In addition, this group exhibited a significant increase in the apolipoprotein A-I, ghrelin, and high-density lipoprotein cholesterol levels. The energy metabolic factors that influenced the visceral fat included ghrelin, leptin, insulin, glucose, and HOMA-IR. The t-value, which determined the statistical significance of the independent variables, was significant for ghrelin, glucose, insulin, and HOMA-IR (p < 0.05). Regular and continuous aerobic exercise (e.g., line dancing) effectively improved the body composition, visceral fat, serum blood lipids, leptin, ghrelin, and HOMA-IR factors in obese postmenopausal Korean women.

Effects of SNP Markers of the Apolipoprotein E (APOE) Gene on Meat Quantity and Quality Traits in Korean Cattle (한우 아포지단백질 E (APOE) 유전자의 SNP Marker가 육량 및 육질형질에 미치는 영향)

  • Shin, Ki-Hyun;Shin, Sung-Chul;Chung, Ku-Young;Chung, Eui-Ryong
    • Food Science of Animal Resources
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    • v.29 no.1
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    • pp.108-113
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    • 2009
  • Apolipoprotein E (APOE) is a plasma lipoprotein in mammals and plays an important role in the transport and metabolism of lipids such as phospholipids and triglycerides. Therefore, the APOE gene could be a candidate gene controlling lipid metabolism in beef cattle. This study was performed to identify single nucleotide polymorphisms (SNP) in the APOE gene and to investigate the effects of SNP genotype on the carcass traits such as meat quantity and quality in Korean cattle. For PCR amplification, pooled DNA made from unrelated 60 individuals was prepared and primer pairs were designed based on the cDNA sequence of exon 4 region of the bovine APOE gene. A SNP was identified at position 2034 (T/C substitution) of the exon 4 region in the APOE gene. PCR-RFLP procedure with restriction enzyme ACC I was developed for determining the SNP genotype for each of a total of 309 animals with pedigree information and performance records through the national progeny testing program. The frequencies of the genotypes TT, TC and CC were 10.9, 46.9 and 42.2%. Gene frequencies were 0.344 for T allele and 0.656 for C allele. The g.2034T>C SNP genotype showed a significant effect (p<0.05) on dressing percentage and meat color, respectively. Animals with the TT genotype showed higher dressing percentage than those with the CC genotype, and TT genotype had desirable meat color compared with CC genotype. These results suggest that the g.2034T>C SNP genotype of the APOE gene may be useful as a DNA marker for meat quantity index and dressing percentage in Korean cattle.

ApoE Allele Test in Korean with Hair Root DNA (모근 DNA를 이용한 한국인의 ApoE 유전자형 검사)

  • Kim, Chong-Ho;Jung, Mi-Ra;Park, Sang-Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.38 no.3
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    • pp.179-183
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    • 2006
  • Alzheimer's disease (AD) is characterised neuropathologically by the accumulation of neuritic plaques and neurofibrillary tangles as well as by cerebrovascular amyloid deposition and neuronal cell loss. Current advances have shown the apolipoproteinE-epsilon 4 (ApoE4) allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of ApoE allele frequencies and dementia remains unknown in populations from many countries. We recently initiated a project to examine ApoE frequencies in non-demented healthy Koreans. Genomic DNA in hair root from a thousand persons was collected and ApoE gene type was investigated with the methods of polymerase chain reaction (PCR) and restriction fragment length polymorphism. A group of a thousand non-demented Koreans over the age of 40 years were found to be positive in 15.7% of the cases for ApoE4. AD and ApoE4 were closely related. ApoE epsilon 4 was a dangerous factor of AD and ApoE 4 allele made a contribution to the heterogenicity of AD.

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Gene Targeting of Low Density Lipoprotein(LDL) Receptor Related Protein 5(LRP5) Involved in the Wnt Signaling Pathway

  • Jeong, Young-Hee;Kim, Suck-Ho;Kim, Dong-Ho;Moon, Seung-Ju;Tokuo Yamamoto;Kang, Man-Jong
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.82-82
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    • 2002
  • The Wnt signaling pathway plays pivotal roles in embryonic development and oncogenesis through various signaling molecules inculding Frizzled receptor, recently characterized LRP5/6 and Dickkopf protein. Although Wnt signaling has been characterized in both developmental and oncogenic processes, little is known about its function in the normal adult. The ability of LRP5 to bind apolipoprotein E(apoE) and the abundant expression of LRP5 transcripts in hepatocytes, raise the possibility that LRP5 plays a role in the hepatic clearance of ApoE-containing chylomicron remonants, a major plasma lipoprotein carrying diet-derived cholesterol. (omitted)

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Effects of the Feral Peach (Prunus persica Batsch var. davidiana Max) Extract on the Lipid Compositions and Blood Pressure Level in Spontaneously Hypertensive Rats (야생 돌복숭아(Prunus persica Batsch var. davidiana Max.) 추출액이 선천성 고혈압 흰쥐의 지질성분 및 혈압 저하에 미치는 영향)

  • Kim, Han-Soo
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1071-1079
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    • 2006
  • The purpose of this study was to observe the effects of the feeding physiological activity substance in feral peach(Prunus Persica Batsch var. davidiana Max.) extract intake on the improvement of the lipid compositions, apolipoprotein and blood pressure level in spontaneously hypertensive rats(SHR, Wistar strain, male) fed the experimental diets for 33 days. Concentrations of total cholesterol, triglyceride(TG), LDL-cholesterol, free cholesterol and atherosclerotic index in serum were significantly lower in the feral peach extract intake groups[groups 5g% Ex.(basal diet+feral peach 5.0g% extract), 10g% Ex.(basal diet+feral peach 10.0g% extract)] than those in the group Control(basal diet+water). In the ratio of HDL-cholesterol concentration to total cholesterol and HDL-cholesterol concentration, feral peach 5.0g%, 10.0g% extract intake groups(group 5g% Ex. and 10g% Ex.) were higher percentage than in the group Control. However, concentrations of total cholesterol and TC in liver and brain were significantly lower in the groups 5g% Ex. and 10g% Ex. than those in the group Control. But the concentrations of apolipoprotein (Apo) A-I and Apo A-II in serum were significantly higher in the feral peach 5.0g% and 10.0g% extract intake groups(5g% Ex. and 10g% Ex.) than in the control group. However, concentrations of Apo C-II, Apo C-III, Apo E and ratio of Apo B to Apo A-I in serum were fairly reduced in the groups 5g% Ex. and 10g% Ex. than in the control group. The levels of systolic and diastolic blood pressure were significantly lower in feral peach 5g% Ex. and 10g% Ex. groups than control group. However, no significance was found in the effect of among the groups(groups 5g% Ex. and 10g% Ex.). From these results, physiological activity substance in feral peach(Prunus persica Batsch var. davidiana Max.) extracts were effective on the improvement of the lipid compositions and cardiovascular heart disease, hypertension in spontaneously hypertensive rats. And particularly, feral peach extracts were more effective as a therapeutic regimen for the control of blood pressure in hypertension.

Periplasmic Expression of a Recombinant Antibody (MabB9) in Escherichia coli

  • Chang, Hae-Choon;Kwak, Ju-Won
    • Journal of Microbiology and Biotechnology
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    • v.7 no.5
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    • pp.299-304
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    • 1997
  • Expression in the periplasm of Escherichia coli of cloned heavy and light chain cDNAs for Fab fragment of a murine monoclonal antibody MabB9 (${\gamma}2b$, K), specific for human plasma apolipoprotein B-100 of LDL, was studied. For the purpose, a vector for two-cistronic expression of the heavy chain cDNA, at the 5' terminus, and light chain cDNA, at the 3' terminus, was constructed using the signal sequences, pelB (for heavy chain) and ompA (for light chain) in a pET vector system. The constructed vector was transformed into E. coli BL21(DE3). The expressed heavy chain (25 kDa) and light chain (23 kDa) of the antibody molecule were detected in total cell extracts as well as in the periplasmic extracts of E. coli.

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