Please use this identifier to cite or link to this item:
標題: 利用多重式微序列法分析敗血症患者基因型
Genotyping of TNF-α, IL-6, IL-10 and IL-18 Genes in Septicemia Patients by Multiplex-Minisequencing
作者: 李威寰
Lee, Wei-Huan
關鍵字: Sepsis;敗血症;Multiplex minisequencing;Single nucleotide polymorphisms;多重式微序列分析法;單一核甘酸多態性
出版社: 動物科學系所
引用: 參考文獻 ACCP/SCCM. 1992. Consensus conference sepsis definition. Crit. Care Med. 20:864-874. Ahrens. P., E. Kattner, B. Kohler, C. Hartel, J. Seidenberg, H. Segerer, J. Moller, and W. Gopel. 2004. Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants. Pediatr. Res. 55:652-656. Aird, W. C. 2003. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 101:3765-3777. Andrejaitiene, J. 2006. The diagnostic value of procalcitonin in severe sepsis. Medicina 42:69-78. Annane, D., E. Bellissant, P. E. Bollaert, J. Briegel, D. Keh, and Y. Kupfer. 2004. Corticosteroids for treating severe sepsis and septic shock. Ann. Emerg. Med. 45:330-332. Arcaroli, J., M. B. Fessler, and E. Abraham. 2005. Genetic polymorphisms and sepsis. Shock 24:300-12. Atan, D., S. J. Turner, D. J. Kilmartin, J. V. Forrester, J. Bidwell, A. D. Dick, and A. J. Churchill. 2005. Cytokine gene polymorphism in sympathetic ophthalmia. Invest. Ophthalmol. Vis. Sci. 46:4245-4250. Balk, R. A., and R. C. Bone. 1989. The septic syndrome. definition and clinical implications. Crit. Care Clin. 5:1-8. Beal, A. L., and F. B. Cerra. 1994. Multiple organ failure syndrome in the 1990s: systemic inflammatory response and organ dysfunction. JAMA. 271:226-233. Bennermo, M., C. Held, S. Stemme, C. G. Ericsson, A. Silveira, F. Green, and P. Tornvall. 2004. Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases? Clin. Chem. 50:2136-2140. Bernard, G. R., J. L. Vincent, P. F. Laterre, S. P. LaRosa, J. F. Dhainaut, A. Lopez-Rodriquez, J. S. Steinqrub, G. E. Garber, J. D. Helterbrand, E. W. Ely, and C. J. Fisher Jr.. 2001. Efficacy and safety of recombinant human activated protein C for severe sepsis. N. Engl. J. Med. 344:699-709. Bone, R. C. 1992. Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA. 268:3453-3455. Boyd, J. H., and K. R. Walley. 2008. Is there a role for sodium bicarbonate in treating lactic acidosis from shock. Curr. Opin. Crit. Care 14:379-383. Bozza, F. A., J. L. Salluh, A. M. Japiassu, M. Soareset, E. F. Assis, R. N. Gomes, M. T. Bozza, H. C. Castro-Faria-Neto, and P. T. Bozza. 2007. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit. Care 11:49. Braun, N., U. Michel, B. P. Ernst, R. Metzner, A. Bitsch, F. Weber, and P. Rieckmann. 1996. Gene polymorphism at position -308 of the tumor- necrosis-factor-α (TNF-α) in multiple sclerosis and its influence on the regulation of TNF-α production. Neurosci. Lett. 215:75-78. Brierley, J., J. A. Carcillo, K. Choong, T. Cornell, A. DeCaen, A. Deymann, A. Doctor, A. Davis, J. Duff, M. A. Dugas, A. Duncan, B. Evans, J. Feldman, K. Felmet, G. Fisher, L. Frankel, H. Jeffries, B. Greenwald, J. Gutierrez, M. Hall, Y. Y. Han, J. Hanson, J. Hazelzet, L. Hernan, J. Kiff, N. Kissoon, A. Kon, J. Irazusta, J. Lin, A. Lorts, M. Mariscalco, R. Mehta, S. Nadel, T. Nguyen, C. Nicholson, M. Peters, R. Okhuysen-Cawley, T. Poulton, M. Relves, A. Rodriguez, R. Rozenfeld, E. Schnitzler, T. Shanley, S. Skache, P. Skippen, A. Torres, B. von Dessauer, J. Weingarten, T. Yeh, A. Zaritsky, B. Stojadinovic, J. Zimmerman, and A. Zuckerberg. 2009. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American college of critical care medicine. Crit. Care Med. 37:666-688 Brookes, A. J. 1999. The essence of SNPs. Gene 234:177-186. Broude, N. E., L. Zhang, K. Woodward, D. Englert, and C. R. Cantor. 2001. Multiplex allele-specific target amplification based on PCR suppression. Proc. Natl. Acad. Sci. U. S. A. 98: 206-211. Calandra, T., J. Gerain, D. Heumann, J. D. Baumgartner, and M. P. Glauser. 1991. High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss- Dutch J5 Immunoglobulin Study Group. Am. J. Med. 91:23-29. Carlet, J., J. Cohen, T. Calandra, S. M. Opal, and H. Masur. 2008. Sepsis: Time to reconsider the concept. Crit. Care Med. 36:964-966. Cederholm, T., M. Persson, P. Andersson, P. Stenvinkel, L. Nordfors, J. Madden, I. Vedin, B. Wretlind, R. F. Grimble, and J. Palmblad. 2007. Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients. J. Intern. Med. 262:215-23. Chamberlain, J. S., R. A. Gibbs, J. E. Ranier, P. N. Nguyen, and C. T. Caskey. 1988. Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res. 16: 11141-11156. Chapman, C. M., J. P. Beilby, S. E. Humphries, L. J. Palmer, P. L. Thompson, and J. Hung. 2003. Association of an allelic variant of interleukin-6 with subclinical carotid atherosclerosis in an Australian community population. Eur. Heart J. 24:1494–9. Conway, D. J., M. J. Holland, R. L. Bailey, A. E. Campbell, O. S. Mahdi, R. Jennings, E. Mbena, and D. C. Mabey. 1997. Scarring trachoma is associated with polymorphism in the tumor necrosis factor α (TNF-α) gene promoter and with elevated TNF-αlevels in tear fluid. Infect. Immun. 65:1003-1006. Damas, P., A. Reuter, P. Gysen, J. Demonty, M. Lamy, and P. Franchimont. 1989. Tumor necrosis factor and interleukin- 1 serum levels during severe sepsis in humans. Crit. Care Med. 17:975-978. Debets, J. M., R. Kampmeijer, M. P. van der Linden, W. A. Buurman, and C. J. van der Linden. 1989. Plasma tumor necrosis factor and mortality in critically ill septic patients. Crit. Care Med. 17:489-494. Dellinger, R. P. 2003. Cardiovascular management of septic shock. Crit. Care Med. 31:946-955. Dellinger, R. P., J. M. Carlet, H. Masur, H. Gerlach, T. Calandra, J. Cohen, J. Gea-Banacloche, D. Keh, J. C. Marshall, M. M. Parker, G. Ramsay, J. L. Zommerman, J. L. Vincent, and M. M. Levy. 2004. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 32:858-873. Dinarello, C. A. 1999. IL-18: a TH1-inducing, pro-inflammatory cytokine and new member of the IL-1 family. J. Allergy. Clin. Immunol. 103:11-24. Dofferhoff, A. S., V. J. Bom, H. G. de Vries-Hospers, J. van Inqen, J. vd Meer, B. P. Hazenberq, P. O. Mulder, and J. Weits. 1992. Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acutephase proteins during the treatment of severe sepsis in humans. Crit. Care Med. 20:185-192. Elnifro, E. M., A. M. Ashshi, R. J. Cooper, and P. E. Klapper. 2000. Multiplex PCR: optimization and application in diagnostic virology. Clin. Microbiol. Rev. 13: 559-570. Emonts, M., J. A. Hazelzet, R. de Groot, and P. W. Hermans. 2003. Host genetic determinants of Neisseria meningitides infections. Lancet Infect. Dis. 3:565-577. Fishman, D., G. Faulds, R. Jeffery, V. Mohamed-Ali, J. S. Yudkin, S. Humphries, and P. Woo. 1998. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic onset juvenile chronic arthritis. J. Clin. Invest. 102:1369-1376. Freeman, B. D., T. G. Buchman, S. McGrath, A. R. Tabrizi, and B. A. Zehnbauer. 2002. Template-directed dye-terminator incorporation with fluorescence polarization detection for analysis of single nucleotide polymorphisms implicated in sepsis. J. Mol. Diagn. 4:209-215. Friedman, G., E. Silva, and J. L. Vincent. 1998. Has the mortality of septic shock changed with time? Crit. Care Med. 26:2078-2086. Gebhard, F., H. Pfetsch, G. Steinbach, W. Strecker, L. Kinzl, and U. B. Bruckner. 2000. Is interleukin 6 an early marker of injury severity following major trauma in humans? Arch. Surg. 135:291-295. Giedraitis, V., B. He, W. X. Huang, and J. Hillert. 2001. Cloning and mutation analysis of the human Il-18 promoter: a possible role of polymorphisms in expression regulation. J. Neuroimmunol. 112:146-152. Girardin, E. P., M. E. Berner, G. E. Grau, S. Suter, G. Lacourt, and L. Paunier. 1990. Serum tumour necrosis factor in newborns at risk for infections. Eur J Pediatr. 149:645-647. Gwee, P. C., K. Tang, J. M. Chua, E. J. Lee, S. S. Chong, and C. G. Lee. 2003. Simultaneous genotyping of seven single-nucleotide polymorphisms in the MDR1 gene by single-tube multiplex minisequencing. Clin. Chem. 49:672-676. Hedberg, C. L., K. Adcock, J. Martin, J. Loggins, T. E. Kruger, and R. J. Baier. 2004. Tumor necrosis factor α -308 polymorphism associated with increased sepsis mortality in ventilated very low birth weight infants. Pediatr. Infect. Dis. J. 23:424-8. Hill, A. V. 1999. Genetics and genomics of infectious disease susceptibility. Br Med Bull 24:381-384. Hoffmann, S. C., E. M. Stanley, E. D. Cox, B. S. DiMercurio, D. E. Koziol, D. M. Harlan, A. D. Kirk, and P. J. Blair. 2002. Ethnicity greatly influences cytokine gene polymorphism distribution. Am. J. Transplant. 2:560-567. Howes, L. G., and D. G. Brillante. 2008. Expert opinion on tilarginine in the treatment of shock. Expert Opin. Investig. Drugs 17:1573-1580. Irazuzta, J. K. J. Sullivan, P. C. Garcia, and J. P. Piva. 2007. Pharmacologic support of infants and children in septic shock. J. Pediatr. 83:36-45. Jones, S. A. 2005. Directing transition from innate to acquired immunity: Defining a role for IL-6. J. Immunol. 175:3463-3468. Jovanovic, Z., M. Ilic, and S. Jankovic. 2007. Pathogenic mechanisms in the development of surgical site infections. Med. Pregl. 60:30-50. Kidokoro, A., T. Iba, M. Fukunaga, and Y. Yagi. 1996. Alterations in coagulation and fibrinolysis during sepsis. Shock 5:223-228. Kroeger, K. M., K. S. Carville, and L. J. Abraham. 1997. The -308 tumor necrosis factor-α promoter polymorphism effects transcription. Mol. Immunol. 34:391-399. Kubaszek, A., J. Pihlajamaki, K. Punnonen, P. Karphapaa, I. Vauhkonen, and M. Laakso. 2003. The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity. Diabetes 52:558-561. Kumar, A., J. Short, and J. E. Parrillo. 1999. Genetic factors in septic shock. J Am Med Assoc 282:579-581. Lech-Maranda, E., L. Baseggio, J. Bienvenu, C. Charlot, F. Berger, D. Rigal, K. Warzocha, B. Coiffier, and G. Salles. 2004. Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. Blood 103:3529-3534. Levi, M., T. van der Poll, H. ten Cate, and S. J. van Deventer. 1997. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia. Eur. J. Clin. Invest. 27:3-9. Lorente, J. A., L. J. Garcia-Frade, L. Landin, R. de Pablo, C. Torrado, E. Renes, and A. Garcia-Avello. 1993. Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 103:1536-1542. Louis, E., D. Franchimont, A. Piron, Y. Gevaert, N. Schaaf-Lafontaine, S. Roland, P. Mahieu, M. Malaise, D. De Groote, R. Louis, and J. Belaiche. 1998. Tumour necrosis factor (TNF) gene polymorphism influences TNF-α production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin. Exp. Immunol. 113:401-406. Markoulatos, P., N. Siafakas, and M. Moncany. 2002. Multiplex polymerase chain reaction: a practical approach. J. Clin. Lab. Anal. 16: 47-51. Matsuda, K., H. Hirasawa, S. Oda, H. Shiga, and K. Nakanishi. 2001. Current topics on cytokine removal technologies. Ther. Apher. 5:306-314. Matsuda, N. and Y. Hattori. 2006. Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J. Pharmacol. Sci. 101:189-198. Mayr, H. W., K. Vierlinger, R. Pichler, A. Kriegner, A. M. Hirschl, E. Presterl, L. Bodrosssy, and C. Noehammer. 2007. Identification of human pathogens isolated from blood uusing microarray hybridization and signal pattern recognition. B.M.C. Microbiology. 7:78-94. McCuskey, R. S., R. Urbaschek, and B. Urbaschek. 1996. The microcirculation during endotoxemia. Cardiovasc. Res. 32:752-763. Mira, J. P., A. Cariou, F. Grall, C. Delclaux, M. R. Losser, F. Heshmati, C. Cheval, M. Monchi, J. L. Teboul, F. Riche, G. Leleu, L. Arbibe, A. Mignon, M. Delpech, and J. F. Dhainaut. 1999. Association of TNF2, a TNF-a promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. J. Am. Med. Assoc. 282:561-568. Moerer, O. and H. Burchardi. 2006. The cost of sepsis. Anaesthesist 55:36-42. Molvig, J., F. Pociot, H. Worsaae, L. D. Wogensen, L. Baek, P. Christensen, T. Mandrup-Poulsen, K. Andersen, P. Madsen, J. Dyerberg, and J. Nerup 1991. Dietary supplementation with omega-3-polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin-1b content but not monokine secretion in healthy and insulin-dependent diabetic individuals. Scand. J. Immunol. 34:399-410. Mueller, C., A. Maisel, A. Mebazaa, and G. S. Filippatos. 2008. The use of B-type natriuretic peptides in the intensive care unit. Congest. Heart Fail. 14:43-45. Nadel, S., M. J. Newport, R. Booy, and M. Levin. 1996. Variation in the tumor necrosis factor-α gene promoter region may be associated with death from meningococcal disease. J. Infect. Dis. 174:878–880. Natanson, C., C. J. Esposito, and S. M. Banks. 1998. The sirens'' song of confirmatory sepsis trials: selection bias and sampling error. Crit. Care Med. 26:1927-1931. Nicod, L. P., F. el Habre, J. M. Dayer, and N. Boehringer. 1995. Interleukin-10 decreases tumor necrosis factor alpha and beta in alloreactions induced by human lung dendritic cells and macrophages. Am. J. Respir. Cell Mol. Biol. 13:83-90. Olson, N. C., P. W. Hellyer, and J. R. Dodam. 1995. Mediators and vascular effects in response to endotoxin. Br. Vet. J. 151:489-522. Orita, M., H. Iwahana, H. Kanazawa, K. Hayashi, and T. Sekiya. 1989. Detection of polymorphism of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc. Natl. Acad. Sci. USA 86:2766-2770. Panacek, E. A., and M. Kaul. 1999. IL-6 as a marker of excessive TNF-α activity in sepsis. Sepsis 3:65-73. Papathanassoglou, E. D., J. A. Moynihan, and M. H. Ackerman. 2000. Does programmed cell death (apoptosis) play a role in the development of multiple organ dysfunction in critically ill patients? Crit. Care Med. 28:537-549. Parrello, T., G. Monteleone, S. Cucchiara, I. Monteleone, L. Sebkova, P. Doldo, F. Luzza, and F. Pallone. 2000. Up-regulation of the IL-12 receptor beta 2 chain in Crohn’s disease. J. Immunol. 165:7234-7239. Rau, B., K. Baumgart, A. S. Paszkowski, J. M. Mayer, and H. G. Beger. 2001. Clinical relevance of caspase-1 activated cytokines in acute pancreatitis: high correlation of serum IL-18 with pancreatic necrosis and systemic complications. Crit. Care Med. 28:1556-1562. Remick, D. G., G. R. Bolgos, J. Siddiqui, J. Shin, and J. A. Nemzek. 2002. Six at six: Interleukin-6 measured 6h after the initiation of sepsis predicts mortality over 3 days. Shock 17:463-467. Reynard, M. P., D. Turner, and C. V. Navarrete. 2000. Allele frequencies of polymorphisms of the tumour necrosis factor-α, interleukin-10, interferon-γ and interleukin-2 genes in a North European Caucasoid group from the UK. Eur. J. Immunogenet. 27:241-249. Roman, J., F. Fernandez, F. Velasco, R. Rojas, M. R. Roldan, and A. Torres. 1993. Serum TNF levels in neonatal sepsis and septic shock. Acta. Paediatr. 82:352-354. Sablotzki, A., J. Muhling, and E. Czeslick. 2005. Sepsis and multiple organ failure - update of current therapeutic concepts. AINS. 40:511-520. Santos, A. A., J. L. Browning, M. R. Sceltinga, E. A. Lynch, E. F. Brown, P. Lawton, E. Chambers, I. Dougas, C. D. Benjamin, C. A. Dinarello, S. M. Wolff, D. O. Jacobs, and D. W. Wilmore. 1994. Are events after endotoxemia related to circulating phospholipase A2? Ann. Surg. 219:183-192. Schaaf, B. M., F. Boehmke, H. Esnaashari, U. Seitzer, H. Kothe, M. Maass, P. Zabel, and K. Dalhoff. 2003. Pneumococcal septic shock is associated with the interleukin-10-1082 gene promoter polymorphism. Am. J. Respir. Crit. Care Med. 168:476-480. Schluter, B., C. Raufhake, M. Erren, H. Schotte, F. Kipp, S. Rust, H. Van Aken, G. Assmann, and E. Berendes. 2002. Effect of the interleukin-6 promoter polymorphism (-174 G/C) on the incidence and outcome of sepsis. Crit. Care Med. 30:32-37. Schoske, R., P. M. Vallone, C. M. Ruitberg, and J. M. Butler. 2003. Multiplex PCR design strategy used for the simultaneous amplification of 10 Y chromosome short tandem repeat (STR) loci. Anal. Bioanal. Chem. 375:333-343. Schroder, J., V. Kahlke, M. Book, and F. Stuber. 2000. Gender differences in sepsis: genetically determined? Shock 14:307-310. Sessler, C. N. and W. Shepherd. 2002. New concepts in sepsis. Curr. Opin. Crit. Care 8:465-472. Settanni, L., and A. Corsetti. 2007. The use of multiplex PCR to detect and differentiate food- and beverage-associated microorganisms: a review. J. Microbiol. Methods 69: 1-22. Sibbald, W. J. 1976. Sepsis--the Wayne State University Symposium--part III. Bacteremia and endotoxemia: a discussion of their roles in the pathophysiology of gram-negative sepsis. Heart Lung 5:765-771. Sobrino, B., M. Brion, and A. Carracedo. 2005. SNPs in forensic genetics: a review on SNP typing methodologies. Forensic Sci. Int. 154: 181-194. Standl, T. 2007. Abdominal compartment syndrome. A still underestimated problem. AINS. 42:500-503. Stassen, N. A., C. M. Breit, L. A. Norfleet, and H. C. Polk Jr.. 2003. IL-18 promoter polymorphisms correlate with the development of post-injury sepsis. Surgery 134:351-356. Stratil, A., L. Peelman, M. Van Poucke, and S. A. Cepica. 1997. A HinfI PCR-RFLP at the porcine leptin (LEP) gene. Anim. Genet. 28:371-372. Stuber, F., M. Peterson, F. Bokelmann, and U. Schade. 1996. A genomic polymorphism within the tumor necrosis factor locus influences plasma concentrations and outcome of patients with severe sepsis. Crit. Care Med. 24:381-384. Strieter, R. M., S. L. Kunkel, and R. C. Bone. 1993. Role of tumor necrosis factor- alpha in disease states and inflammation. Crit. Care Med. 21:447-463. Suto, R., and P. K. Srivastava. 1995. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269:1585-1588. Suzuki, T., K. Koike, Y. Shibata, R. Yoshida, J. Ai-boshi, S. Kushimoto, et al.. 2002. Serum interleukin-18 measured in trauma patients. Surg. Infect. 3:92. Syvanen, A. C. 2001. Accessing genetic variation: genotyping single nucleotide polymorphisms. Nat. Rev. Genet. 2: 930-942. Takao, K., J. Cheng, and K. R. Mitchelson. 2001. Magnetic bead-isolated single-strand DNA for SSCP analysis. Methods Mol. Biol. 163:135-147. Tang, G. J., S. L. Huang, H. W. Yien, W. S. Chen, C. W. Chi, C. W. Wu, W. Y. Lui, J. H. Chiu, and T. Y. Lee. 2000. Tumor necrosis factor gene polymorphism and septic shock in surgical infection. Crit. Care Med. 28:2733-2736. Terry, C. F., V. Loukaci, and F. R. Green. 2000. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J. Biol. Chem. 275:18138–18144. Thomassen, M. J., L. T. Divis, and C. J. Fisher. 1996. Regulation of human alveolar macrophage inflammatory cytokine production by interleukin- 10. Clin. Immunol. Immunopathol. 80:321-324. Torres, A., T. Bentley, J. Bartels, J. Sarkar, D. Barclay, R. Namas, G. Constantine, R. Zamora, J. C. Puyana, and Y. Vodovotz. 2008. Mathematical modeling of post-hemorrhage inflammation in mice: studies using a novel, computer-controlled, closed-loop hemorrhage apparatus. Shock. (In Press) Turnbull, I. R., P. Javadi, T. G. Buchman, R. S. Hotchkiss, I. E. Karl, and C. M. Coopersmith. 2004. Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels. Shock 21:121-125. van Deuren, M., A, S. Dofferhoff, and J. W. van der Meer. 1992. Cytokines and the response to infection. J. Pathol. 168:349-356. van Deventer, S. J., H. R. Buller, J. W. ten Cate, L. A. Aarden, C. E. Hack, A. Sturk. 1990. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood. 76:2520-2526. Vandijck, D., J. M. Decruvenaere, and S. I. Blot. 2006. The value of sepsis definitions in daily ICU-practice. Acta Clin. Belg. 61:220-226. Vervloet, M. G., L. G. Thijs, and C. E. Hack. 1998. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin. Thromb. Hemost. 24:33-44. Vianna, R. C., R. N. Gomes, F. A. Bozza, R. T. Amancio, P. T. Bozza, C. M. David, and H. C. Castro-Faria-Neto. 2004. Antibiotic treatment in a murine model of sepsis: impact on cytokines and endotoxin release. Shock 21:115-120. Vignal, A., D. Milan, M. Sancristobal, and A. Eggen. 2002. A new on SNP and other types of molecular markers and their use in animal genetic. Genet. Sel. Evol. 34: 275-305. Villar, J., N. M. Meyer, L. P. Mendes, and C. Flores. 2004 Bench-to-bedside review: Understanding genetic predisposition to sepsis. Critical Care. 8:180-189. Vincent, J. L. 1998. Cardiovascular alterations in septic shock. J. Antimicrob. Chemother. 41:9-15. Vincent, J. L., and M. Zambon. 2006. Why do patients who have acute lung injury/acute respiratory distress syndrome die from multiple organ dysfunction syndrome? Implications for management.” Clin. Chest Med. 27:725-731. Vozarova, B., J. M. Fernandez-Real, W. C. Knowler, L. Gallart, R. L. Hanson, J. D. Gruber, W. Ricart, J. Vendrell, C. Richart, P. A. Tataranni, and J. K. Wolford. 2003. The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in Native Americans and Caucasians. Hum. Genet. 112:409-413. Wang, P., P. Wu, M. I. Siegel, R. W. Egan, and M. M. Billah. 1995. Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J. Biol. Chem. 270:9558-9563. Watanabe, E., H. Hirasawa, S. Oda, H. Shiqa, K. Matsuda, M. Nakamura, R. Abe, and T. Nakada. 2005. Cytokine-related genotypic differences in peak interleukin-6 blood levels of patients with SIRS and septic complicaqtions. J. Trauma 59:1181-1189. Westendorp, R. G., J. A. Langermans, C. E. de Bel, A. E. Meinders, J. P. Vandenbroucke, R. van Furth, and J. T. van Dissel. 1995. Release of tumor necrosis factor: an innate host characteristic that may contribute to the outcome of meningococcal disease. J. Infect. Dis. 171:1057-60. Westendorp, R. G., J. A. Langermans, T. W. Huizinga, C. L. Verweij, and A. Sturk. 1997. Genetic influence on cytokine production in meningococcal disease. Lancet 349:1912-1913. Wilson, A. G., F. S. di Giovine, A. I. Blakemore, and G. W. Duff. 1992. Single base polymorphism in the human tumour necrosis factor α (TNFα) gene detectable by NcoI restriction of PCR product. Hum. Mol. Genet. 1:353. Wilson, A. G., J. A. Symons, T. L. McDowell, H. O. McDevitt, and G. W. Duff. 1997. Effects of a polymorphism in the human tumor necrosis factor a promoter on transcriptional activation. Proc. Natl. Acad. Sci. U.S.A. 94:3195-3199. Wjst, M. 2004. Target SNP selection in complex disease association studies. BMC Bioinformatics 5:92. Wunder, C., O. Eichelbronner, and N. Roewer. 2004. Are IL-6, IL-10 and PCT plasma concentrations reliable for outcome prediction in severe sepsis? A comparison with APACHE III and SAPS II. Inflamm. Res. 53:158-163.
本試驗之目的在探討人類基因單一核甘酸多態性與敗血症患者發炎反應性狀之相關性,分析包含於人類腫瘤壞死因子α (tumor necrosis factor-α,TNF-α)、介白素-6 (interleukin-6,IL-6)、介白素-10 (interleukin-10,IL-10)及介白素-18 (interleukin-18,IL-18)等四個候選基因的七個基因型。先以軟體設計專一性引子對,經過PCR反應增殖標的DNA後,分別以PCR-SSCP、PCR-RFLP、微序列法與多重式微序列法進行基因型鑑定。建立以多重式微序列法開發出能於單一試管內同時鑑定多個SNPs標記之DNA檢測平台,檢測之結果與其他方法相符,顯示多重式微序列分析法之可靠性。以此方法檢測之結果分析台灣署立南投醫院重症加護病房敗血症患者各基因之基因型與交替基因頻率分佈,結果發現在TNF-α基因G-308A的GG基因型患者其存活天數以及存活率皆優於GA型,故知G交替基因有利存活;IL-6基因G-174C的GG基因型患者其存活天數以及存活率皆優於GC型,故知G交替基因有利存活;IL-10基因G-1082A的AA基因型患者其存活率優於GA型,故知A交替基因有利存活;IL-18基因之基因型同時為C-607A與G-137C雜合型之患者擁有最高的存活率,且各基因中較有利於存活的基因型亦符合已發表文獻之研究結果。進一步探討台灣署立南投醫院重症加護病房敗血症患者各性狀與臨床觀察指標、基因型存活率之相關性,結果發現TNF-α基因G-308A的GG型患者較之GA型患者、IL-6基因G-174C的GG型患者較之GC型患者、IL-10基因G-1082A的AA型患者較之GA型患者,存活率皆顯著較高(p < 0.05)。TNF-α基因G-308A的GA型患者其第一天血中IL-10濃度遠較GG型患者高(p < 0.05);肌酸酐 (creatinine)也高出GG型患者2倍以上(p < 0.05),顯示腎功能極差,呼應先前文獻指出GA型患者死亡率較高之結果。本試驗建立之多重式微序列分析法以一毛細管同時檢測多個基因的方法,較之傳統的單一核甘酸檢測方法,具有快速、正確及降低成本等優勢,應可應用於人體或動物生理病理特性之相關分析。

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) with traits relative to inflammatory process in septicemia patients. Genotyping of TNF-α, IL-6, IL-10 and IL-18 genes were carried out by PCR-SSCP, PCR-RFLP, minisequencing and multiplex minisequencing. Specific primer pairs were designed by GCG sequence analysis software and each of the target genes was amplified. The results showed that the multiplex-minisequencing method was able to unambiguously and simultaneously genotyping many SNP loci in one microtubes. Genotypic and allelic frequencies of each gene were analyzed. The results revealed that the survival day and survival rate of GG type of TNF-α (G-308A), GG type of IL-6 (G-174C) were better than the other types in septic patients in the Nantou Hospital. The survival rate of AA type of IL-10 (G-1082A) was higher than GA type. Patients with both of CA type of IL-18 (C-607A) and GC type of IL-18 (G-137C) have the highest survival rate. According to above evidence revealed G allele of TNF-α (G-308A), G allele of IL-6 (G-174C) and A allele of IL-10 (G-1082A) were most advantageous for survival. Patients with GG type of TNF-α (G-308A), GG type of IL-6 (G-174C), and AA type of IL-10 (G-1082A) have a higher survival rate than other types (p <0.05). Patients with GA type of TNF-α (G-308A) have a higher serum IL-10 level at entry (p < 0.05). These patients also have doubled serum creatinine represents poor renal functions than GG type patients. It may be one reason for higher mortality happened to GA type patients revealed from previous studies. We have successfully developed a rapid, accuracy and cost-effective for genotyping many loci in the same capillary tube. These results could be useful for human body or animal physiological and pathological analysis.
其他識別: U0005-2607200910593600
Appears in Collections:動物科學系

Show full item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.