• Title/Summary/Keyword: Molecular medicine

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Effect of Epidural Morphine and Bupivacaine with Hypertonic Solution or the Duration of Analgesia (경막외 Morphine, Bupivacaine 및 고장성용액 혼주시 진통지속효과에 미치는 영향)

  • Park, Wook;Park, Kwang-Won
    • The Korean Journal of Pain
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    • v.1 no.1
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    • pp.64-73
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    • 1988
  • Recent studios have shown that narcotic drags produce an unusually intense, prolonged and segmental analgesic action in man whoa injected into the spinal subarachnoid or epidural space (Wang et al, 1979; Behar et al, 1979; Cousins et al, 1979; Magora et a., 1980, Johnston and McCaughey, 1980). Since 1960, many investigators claimed that low molecular weight(LMW) dextran increased the clinical duration of lidocaine(Loder, 1960; Loder, 1962), tetracaine (Chinn and Wirjoatmadja, 1967) and bupivacaine(Kaplan et al, 1975) in man but the mechanism of the action of dextran was unclear. But Curtiss and Scurlock(1979), and Buckled and Fink(1979) claimed that LMW dextran has no effect on the duration of action of bupivacaine in animal studies. The present study was performed to evaluate the clinical efficacy of analgesia by the thoracic epidural injection of morphine and bupivacaine mixture for the relief of pain due to fractured or contused ribs, to evaluate the duration of analgesic effect by the use of the above mixture in a hypertonic solution(dextran 70 or 50% dextrose in water) and to observe the possibility of improvement in the lung function after the pain block. The complications following the pain block were also observed. The 50 single thoracic epidural injections of the mixture were divided into three groups : Group 1(n=15) served as a control group and drags used for the relief of pain were as follows(Mean$\pm$S.D.): morphine($2.13{\pm}1.64\;mg$), 0.5% bupivacaine($3.10{\pm}1.04\;ml$) and 0.9% saline($3.64{\pm}1.11\;ml$). Group 2(n=16) serves as an experimental group and drugs were as follows(Mean$\pm$S.D.): morphine($2.13{\pm}0.72\;mg$), 0.5% bupivacaine($3.06{\pm}0.77\;ml$) and dextran 70($3.75{\pm}1.29\;ml$). Group 3 (n=19) served as an experimental group and drags were as follows(Mean$\pm$S.D.) : morphine($2.42{\pm}0.51\;mg$), 0.5% bupivacaine($3.21{\pm}0.71\;ml$) and 50% dextrose in water($3.58{\pm}1.11\;ml$). The results are were follows: 1) The Dumber of patients who obtained excellent and good analgesic effects following the block were greater in the experimental Croup 2(94%) and Group 3 (90%) than theme of the control Group 1 (80%). 2) The duration of pain relief which lasted more than 3 days after the epidural block was longer in the experimental Group 2 (81%) and Group 3 (75%) than those of the control Croup 1(67%). 3) The pulmonary reserve(FVC%+FEV 1.0%) of 27 cases who were treated by the pain block between 1 and 31 drys following the chest injury was increased to about 13% than those before the block, and that of 13 cases between 32 and 82 days following the chest injury was decreased to about 4% than those before the block. 4) Of the complications following the pain block, there were 5 cased(10%) of nausea within 2 hours following the block, 4 cases(8%) of vomiting after 2 hours following the block, 10 cases(20%) of pruritus after 3~4 hours following the block, 17 cases(34%) of transient urinary retention which tasted 8 to 19 hours, 3 cases(6%) of headache within 2 hoers following the block and 2 cases(4%) of dural puncture. In conclusion, it is suggested that the clinical duration of analgesic effect produced by morphine and bupivacaine mixture can be prolonged by addition of the hypertonic solution to the mixture.

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Molecular Genetic Analysis of Behcet's Disease in Korean (한국인 베체트 환자의 분자유전학적 연구)

  • Park, Sang-Bum;Nam, Youn-Hyoung;Park, Su-Min;Lee, Sang-Hyun;Ahn, Young-Chang;Cho, Min-Ho;Kim, Jong-Gyu;Choi, Jae-Gu;Kim, Seong-Kyu;Jang, Won-Cheoul
    • Journal of the Korean Chemical Society
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    • v.51 no.6
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    • pp.536-542
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    • 2007
  • Behcet's disease (BD) is a chronic inflammatory disorder, involving several organs. Inflammation in the disease is thought to be mediated by cytokines derived from T-helper type 1 (Th1) lymphocytes. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. It is noted that multiple genes, including MHC (major histocompatibility complex) and non-MHC genes, are implicated in the pathogenesis of BD. This study tries to determine whether HLA-B51, IL-18, SLC11A1 and TNF-α polymorphisms are associated with susceptibility to Behcet's disease in Koreans. As a results, HLA-B51 was a genetic factor with the strongest association with BD. But it is still uncertain whether this HLA molecule is directly involved in the pathogenesis of BD. Although the IL-18 gene polymorphisms were not associated with a susceptibility to BD in the Korean population, the patients carrying the GG genotype at position 137 had a higher risk of developing the ocular lesions. This study suggests that the allele 3 and the genotype allele 3 / allele 3 of 5'-promoter (GT)n polymorphism in the SLC11A1 gene may have a protective effect for the development of BD in the Korean population. There were no evidences for genetic association conferred by the TNF-α gene with respect to susceptibility to BD.

JSAP1 Interacts with Kinesin Light Chain 1 through Conserved Binding Segments (JSAP1과 Kinesin Light Chain 1의 결합 및 결합부위 규명)

  • Kim, Sang-Jin;Lee, Chul-Hee;Park, Hye-Young;Yea, Sung-Su;Jang, Won-Hee;Lee, Sang-Kyeong;Park, Yeong-Hong;Cha, Ok-Soo;Moon, Il-Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.17 no.7 s.87
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    • pp.889-895
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    • 2007
  • A conventional kinesin, KIF5/kinesin-I, is composed of two kinesin heavy chains (KHCs) and two kinesin light chains (KLCs) and binds directly to microtubules. KIF5 motor mediates the transport of various membranous organelles, but the mechanism how they recognize and bind to a specific cargo has not yet been completely elucidated. Here, we used the yeast two-hybrid system to identify the neuronal protein(s) that interacts with the tetratricopeptide repeats (TRP) of KLCI and found a specific interaction with JNK/stress-activated protein kinase-associated protein 1 (JSAP1/JIPP3). The yeast two-hybrid assay demonstrated that the TRP 1,2 domain-containing region of KLCI mediated binding to the leucine zipper domain of JSAP1. JSAP1 also bound to the TRP region of lac2 but not to neuronal KIF5A, KIF5C and ubiquitous KIF5B in the yeast two-hybrid assay. In addition, these proteins showed specific interactions in the GST pull-down assay and by co-immunoprecipitation. KLCI and KIF5B interacted with GST-ISAP1 fusion proteins, but not with GST alone. An antibody to JSAPI specifically co-immunoprecipitated KIF5s associated with JSAP1 from mouse brain extracts. These results suggest that JSAP1, as KLC1 receptor, is involved in the KIF5 mediated transport.

Genotypic and Phenotypic Characteristics of Staphylococcus aureus Isolates from Lettuces and Raw Milk (상추와 원유에서 분리한 황색 포도상구균의 유전형 및 표현형 특징)

  • Jung, Hye-Jin;Cho, Joon-Il;Park, Sung-Hee;Ha, Sang-Do;Lee, Kyu-Ho;Kim, Cheol-Ho;Song, Eun-Seop;Chung, Duck-Hwa;Kim, Min-Gon;Kim, Kwang-Yup;Kim, Keun-Sung
    • Korean Journal of Food Science and Technology
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    • v.37 no.1
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    • pp.134-141
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    • 2005
  • To characterize genotypic and phenotypic traits of Staphylococcus aureus isolates (n = 86) from lettuces and raw milk, major virulence-associated genes and antibiotic susceptibility were detected using PCR-based methods and disk diffusion method, respectively. All isolates possessed coagulase gene and showed five polymorphism types [500 bp (2.4%), 580 bp (17.4%), 660 bp (61.6%), 740 bp (17.4%), and 820 bp (1.2%)] due to variable numbers of tandem repeats present within the gene. Two or three different loci of hemolysin gene family were dominant in isolates, 47 of which (55%) possessed combination of hla/hld/hlg-2 genes as the most prevalent types. Among enterotoxin-encoding genes, sea was detected from 32 isolates (37%), sed from 1 isolate (1%), and sea and sed genes were co-detected from 4 isolates (5%), whereas seb, sec, and tsst-1 genes were not detected. All isolates were susceptible to ciprofloxacin, trimethoprim/sulfamethoxazole, oxacillin, and vancomycin, 85 isolates (99%) to penicillin G, 54 isolates (63%) to chloramphenicol, 51 isolates (59%) to erythromycin, and 7 isolates (8%) to clindamycin. Among resistant isolates, seven displayed multiantibiotic-resistance against two different antibiotics.

Mutations of p53 Tumor Suppressor Gene in Human Lung Cancer Cell Lines (사람 폐암세포주에서 p53 종양억제유전자의 변이)

  • Hong, Weon-Seon;Hong, Seok-Il;Lee, Dong-Soon;Son, Young-Sook;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.6
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    • pp.653-658
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    • 1993
  • Background: Recent advancement of molecular genetics has revealed that malignant transformation of a cell may be a complex multistep process and this process is grouped, in general, into two distinct categories, activation of protooncogenes and inactivation of tumor suppressor genes. This study was focused on the mutation of p53 tumor suppressor gene, because p53 gene mutation is now generally accepted to be one of the most frequent genetic changes in a variety of human cancers. Although lung cancer is one of the common cancers in Korea, the genetic change in the carcinogenesis process is not yet known clearly. To investigate the role of p53 gene mutation in lung cancer, we examined the mutations of exon 4-8 of the p53 gene in humna lung cancer cell lines, because most of the mutations of p53 gene have been reported to develop in exon 4-8. Method: Genomic DNA was obtained by the digestion of proteinase K and the extraction by phenol-chloroform-ethanol method from two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and one human small cell lung cancer cell line, H69. To detect the mutations of exon 4-8 of the p53 gene, polymerase chain reaction single-strand conformation polymorphism(PCR-SSCP) analysis was performed with the DNA extracted from the cells. Results: The mutation of p53 gene was present in all three cell lines tested. In PC-9, PC-14 and H69, the altered mobility was detected in exon 7, 7 and 5, respectively. Conclusion: These results suggest that p53 gene mutation plays an important role in certain steps of the carcinogenesis of human non-small cell and small cell lung cancer.

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Comparison of the Results for Sentinel Lymph Node Mapping in the Breast Cancer Patients using $^{99m}Tc$-Antimony Trisulfide Colloid, $^{99m}Tc$-Tin Colloid, and $^{99m}Tc$-Human Serum Albumin (유방암 환자에서 $^{99m}Tc$-Antimony Trisulfide Colloid, $^{99m}Tc$-Tin Colloid, $^{99m}Tc$-Human Serum Albumin을 이용한 감시림프절 매핑 성적의 비교)

  • Jang, Sung-June;Moon, Seung-Hwan;Kim, Seok-Ki;Kim, Bom-Sahn;Kim, Seok-Won;Chung, Ki-Wook;Kang, Keon-Wook;Lee, Eun-Sook
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.6
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    • pp.546-552
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    • 2007
  • Purpose: In the breast cancer patient, lymphatic mapping and sentinel lymph node biopsy are the most important procedure for axillary lymph node staging. We aimed to compare the three radiocolloids [$^{99m}Tc$-antimony trisulfide colloid (ASC), $^{99m}Tc$-tin colloid (TC), and $^{99m}Tc$-human serum albumin (HSA)] for sentinel lymph node mapping. Subjects and Methods: Totally, 397 patients with clinically N0 stage were enrolled. $^{99m}Tc$-ASC was injected in 202 out of 397 patients, $^{99m}Tc$-TC was injected in 120 patients, and $^{99m}Tc$-HSA was injected in the remaining 75 patients. The sentinel lymph nodes were localized by lymphoscintigraphy and selected using intraoperative gamma probe. All sentinel lymph nodes were investigated by intraoperative pathologic consultation. The axillary lymph nodes which were harvested by the lymph node dissection were also investigated. Results: The patients of each group showed similar clinical characteristics. There were no significant differences (p>0.05) in the identification rate of sentinel lymph nodes (IR), false negative rate (FNR), and negative predictive value (NPV). The axillary lymphadenectomy revealed axillary lymph node metastases in those three groups (ASC-33.2%, TC-31.7%, HSA-22.7%). The IR, FNR, and NPV were not significantly different among those groups. Conclusion: Those three $^{99m}Tc$-labeled radiocolloids showed equivalent results in sentinel lymph node mapping of breast cancer.

Development of Dynamic Kidney Phantom System and its Evaluation of Usability of Application in Nuclear Medicine (핵의학 동적 신장팬텀시스템 개발 적용의 유용성 평가)

  • Park, Hoon-Hee;Lee, Juyoung;Kim, Sang-Wook;Lyu, Kwang Yeul;Jin, Gye Hwan
    • Journal of radiological science and technology
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    • v.36 no.1
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    • pp.49-55
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    • 2013
  • Currently, commercially available phantom can reproduce and evaluate only a static situation, the study is incomplete research on phantom and system which is can confirmed functional situation in the kidney by time through dynamic phantom and blood flow velocity, various difference according to the amount of radioactive. Therefore, through this study, it has produced the dynamic kidney phantom to reproduce images through the dynamic flow of the kidney, it desires to evaluate the usefulness of nuclear medicine imaging. The production of the kidney phantom was fabricated based on the normal adult kidney, in order to reproduce the dynamic situation based on the fabricated kidney phantom, in this study, it was applied the volume pump that can adjust the speed of blood flow, so it can be integrated continuously radioactive isotopes in the kidney by using $^{99m}Tc$-pertechnate. Used the radioactive isotope was supplied through the two pump. It was confirmed the changes according to the infusion rate, radioactive isotopes and the different injection speeds on the left and right, analysis of the acquired images was done by drawn five times ROI in order to check the reproducibility of each on the front and rear of the kidney and bladder. Depending on the speed of injection, radioisotope was a lot of integrated and emissions up when adjusting the pressure of the pump as 30 stroke, it was the least integrated and emissions up when adjusting as 40 stroke. The integration of the left & right kidney was not reached in the amount of the highest when adjusting as 10 stroke. In the changes according to the amount of the radioactive isotope, 0.6 mCi(22.2 MBq), 0.8 mCi (29.6 MBq)was showed up similar tendency but, in the result of the different injection 0.8 mCi, it was showed up counts close to double of 0.6 mCi. In the result of the differently injection speed of the left & right kidney, as a result of different conditions that injection speed was 20 stroke through left kidney phantom, the injection speed was 30 stroke through right kidney phantom, it was enough difference in the resulting image can be easily distinguished with the naked eye. Through this study, the results showed that the dynamic kidney phantom system is able to similarly reproduce renogram in the actual clinical practice. Especially, the depicted over time for the flow to be excreted through the kidney into the bladder was adequately reproduce, it is expected to be utilized as basic data to check the quality of the dynamic images. In addition, it is considered to help in the field of functional imaging and quality control.

Expression of Cell Cycle Related Genes in HL60 Cells Undergoing Apoptosis by X-irradiation (HL60 세포주에서 방사선 조사에 의한 Apoptosis와 세포 주기 관련 유전자의 발현 변화)

  • Kim, Jin-Hee;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.377-388
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    • 1998
  • Purpose : To evaluate changes in expression of cell cycle related genes during apoptosis induced in HL60 cells by X-irradiation to understand molecular biologic aspects in mechanism of radiation therapy. Material and Methods : HL-60 cell line (promyelocytic leukemia cell line) was grown in culture media and irradiated with 8 Gr by linear accelerator (6 MV X-ray). At various times after irradiation, ranging from 3 to 48 hours were analyzed apoptotic DNA fragmentation assay for apoptosis and by western blot analysis and semi-quantitative RT-PCR for expression of cell cycle related genes (cyclin A, cyclin B, cyclin C, cyclin Dl, cyclin E, cdc2, CDK2, CDK4, $p16^{INK4a}$, $p21^{WAF1}$, $p27^{KIP1}$, E2F, PCNA and Rb). Results : X-irradiation (8 Gy) induced apoptosis in HL-60 cell line. Cycline A protein increased after reaching its peak 48 h after radiation delivery and cyclin E, E2F, CDK2 and RB protein increased then decreased after radiation. Radiation induced up-regulation of the expression of E2F is due to mostly increase of Phosphorylated retinoblastoma proteins (ppRb). Cyclin Dl, PCNA, CDC2, CDK4 and $p16^{INK4a}$ protein underwent no significant change at any times after irradiation. There was not detected $p21^{WAF1}$ and $p27^{KIP1}$ protein. Cyclin A, B, C mRNA decreased immediately after radiation and then increased at 12 h after radiation. Cyclin Dl mRNA increased immediately and then decreased at 48 h after radiation. After radiation, cyclin E mRNA decreased with the lapse of time. CDK2 mRNA decreased at 3h and increased at eh after radiation. CDK4 mRNA rapidly increased at 6 to 12 h after radiation. There was no change of expression of $p16^{INK4a}$ and not detected in expressin of $p21^{WAF1}$ and $p27^{KIP1}$ mRNA. Conclusion : We suggest that entry into S phase may contribute to apoptosis of HL60 cells induced by irradiation. Increase of ppRb and decrease of pRb protein are related with radiation induced auoptosis of HL60 cells and tosis of HL60 cells induced by irradiation. Increase of ppRb and decrease of PRb protein are related with radiation induced apoptosis of HL60 cells and this may be associated with induction of E2F and cyclinE/CDK2. These results support that $p21^{WAF1}$ and $p27^{KIP1}$ are not related with radiation induced-apoptosis.

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Immunogenicity of Synthetic Peptide Specific for Major Immunogenic Determinat of Hepatitis B Surface Antigen (B형간염(型肝炎) 표면항원(表面抗原)의 주면역원(主免疫原) 결정기(決定基)에 특이(特異)한 합성(合成) Peptide의 면역원성(免疫原性)에 관한 연구(硏究))

  • Shin, Kwang-soon;Han, Su-nam
    • Korean Journal of Veterinary Research
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    • v.25 no.1
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    • pp.7-17
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    • 1985
  • Many investigators have been pursuing various attempts so far to produce hepatitis B surface antigen(HBsAg) vaccines using the techniques such as isolation from plasma of chronic HBsAg carrier, recombinant DNA technique or preparation of synthetic peptides specific for immunogenic determinants. Hepatitis B virus can not grow on any cell lines by the tissue culture technique at the present time. The plasma of chronic HBsAg carrier is expensive and its source is limited. The HBsAg from the recombinant DNA technique gave still very low yield. Another approach, therefore, has been initiated to develop a synthetic hepatitis B virus vaccine. The possible use of several distinct synthetic vaccines in prophylaxis can be facilitated by availability of full synthetic immunogens. Peptides synthesized for potential application as antiviral vaccines have been mostly tested in the form of conjugates with carrier proteins, although the free synthetic peptide can be immunogenic. To understand basic knowledges on the antigenicity and immunogenicity of a synthetic peptide specific for major immunogenic determinant of HBsAg, a nonapeptide, $H_2N^{139}Cys-Thr-Lys-Pro-Thr-Asp-Gly-^{146}Asn-Aba$ COOH, which corresponds to HBsAg amino acid residues 139 to 147, was synthesized by the Merrifield's solid-phase method with a slight modification. The antigenicity and immunogenicity of this specific synthetic peptide were examined comparing with purified plasma-derived natural HBsAg. The results obtained are as follows; 1. The peptide synthesized showed the identical amino acid composition to the theoretical value. The degree of purification and molecular weight were acertained by methods of high performance liquid chromatography and mass spectrometry. 2. Using m-maleimidobenzoyl-N-hydroxysuccinimide ester as a conjugating agent, the synthetic peptide was conjugated to rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin. Their conjugation yields were 8.3, 9.5, 15.8, 13.5, and 11.2%, respectively. 3. The natural HBsAg was purified from plasma of chronic HBsAg carrier. By the electron microscopic observation of the purified natural HBsAg preparation, no Dane particles were observed and the preparation showed negative DNA polymerase activity. 4. Antigenicity of the synthetic peptide and the plasma-derived natural HBsAg was determined by competition radioimmunoassay using $^{125}I$-natural HBsAg. Their 50% inhibitions appeared as $90{\mu}g/ml$ and $0.12{\mu}g/ml$ for the synthetic peptide and the natural HBsAg, respectively. This indicates that the former was about 750-fold less antigenic than the latter. 5. Immunogenicity of the synthetic peptide was determined by administering the peptide-carrier conjugates into rabbits with and without Freund's complete adjuvant. Regardless the carrier proteins and adjuvant, positive immune responses to the synthetic peptide were observed. The higher antibody titers, however, were shown in the groups administered with Freund's complete adjuvant. 6. Immunizing dose 50% in mice of the various peptide-carrier conjugates was 5.47, 6.00, 65.16, 31.25 and $13.03{\mu}g/dose$ for rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin, respectively, while the natural HBsAg showed $0.65{\mu}g/dose$. 7. It was postulated that homologous proteins prefer to heterologous ones as the carriers.

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Association between MIR149 SNPs and Intrafamilial Phenotypic Variations of Charcot-Marie-Tooth Disease Type 1A (샤르코-마리-투스병 1A형(CMT1A)의 가족내 표현형적 이질성과 MIR149 SNP에 대한 연관성 연구)

  • Choi, Yu Jin;Lee, Ah Jin;Nam, Soo Hyun;Choi, Byung-Ok;Chung, Ki Wha
    • Journal of Life Science
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    • v.29 no.7
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    • pp.800-808
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    • 2019
  • Charcot-Marie-Tooth disease (CMT) is a group of rare peripheral neuropathies characterized by progressive muscle weakness and atrophy and areflexia in the upper and lower extremities. The most common subtype of CMT is CMT1A, which is caused by a tandem duplication of the PMP22 gene in the 17p12 region. Patients with CMT1A show a loose genotype-phenotype correlation, which suggests the existence of secondary genetic or association factors. Recently, polymorphisms of rs71428439 (n.83A>G) and rs2292832 (n.86T>C) in the MIR149 have been reported to be associated with late onset and mild phenotypic CMT1A severity. The aim of this study was to examine the intrafamilial heterogeneities of clinical phenotypes according to the genotypes of these two SNPs in MIR149. For this study, we selected 6 large CMT1A families who showed a wide range of phenotypic variation. This study suggested that both SNPs were related to the onset age and severity in the dominant model. In particular, the AG+GG (n.83A>G) and TC+CC genotypes (n.86T>C) were associated to late onset and mild symptoms. Motor nerve conduction velocity (MNCV) was not related to the MIR149 genotypes. These results were consistent with the previous studies. Therefore, we suggest that the rs71428439 and rs2292832 variants in MIR149 may serve as genetic modifiers of CMT1A intrafamilial phenotypic heterogeneity, as they have a role in the unrelated patients. This is the first study to show an association using large families with variable clinical CMT1A phenotypes. The results will be helpful in the molecular diagnosis and treatment of patients with CMT1A.