Genetic polymorphisms and posttraumatic complications

Wei Gu, Jianxin Jiang, Wei Gu, Jianxin Jiang

Abstract

Major trauma is the leading cause of death in young adults. Despite advances in prehospital system and treatment in hospital, mortality rates have not improved significantly over the past decades. Victims of severe injuries who survive the initial hours have great risk for additional life-threatening complicaitons, including uncontrollable infection (sepsis) and multiple organ dysfunction syndrome (MODS). Single nucleotide polymorphisms (SNPs) have been shown to affect susceptibility to the course of numerous diseases. Accumulating evidence suggests that genetic backgrounds also play important roles in posttraumatic complications. Genetic polymorphisms may become powerful biomarkers for diagnosis and prognosis of trauma-induced complications. Recent advances in studies on associations between genetic polymorphisms and sepsis or MODS have led to better understanding of posttraumatic complications. Here we summarise recent findings on genetic variations in molecules of the innate immune system and other systems as well as their connection with susceptibility to posttraumatic complications.

References

    1. Mackenzie EJ. Epidemiology of injuries: current trends and future challenges. Epidemiologic Reviews. 2000;22(1):112–119.
    1. Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Critical Care Medicine. 2008;36(1):296–327.
    1. Lausevic Z, Lausevic M, Trbojevic-Stankovic J, Krstic S, Stojimirovic B. Predicting multiple organ failure in patients with severe trauma. Canadian Journal of Surgery. 2008;51(2):97–102.
    1. Radojicic C, Andric B, Simovic M, Dujic A, Marinkovic D. Genetic basis of resistance to trauma in inbred strains of mice. Journal of Trauma. 1990;30(2):211–213.
    1. Feng G, Wang Z, Yang Z, et al. Preliminary study on posttrauma-response heterogeneity between c57bl/6 and balb/c inbred mice. Chinese Journal of Traumatology. 2001;5:301–303.
    1. Sorensen TIA, Nielsen GG, Andersen PK, Teasdale TW. Genetic and environmental influences on premature death in adult adoptees. New England Journal of Medicine. 1988;318(12):727–732.
    1. Gudmundsson J, Sulem P, Steinthorsdottir V, et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nature Genetics. 2007;39(8):977–983.
    1. Gudmundsson J, Sulem P, Manolescu A, et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nature Genetics. 2007;39(5):631–637.
    1. Hofmann S, Franke A, Fischer A, et al. Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis. Nature Genetics. 2008;40(9):1103–1106.
    1. Weidinger S, Gieger C, Rodriguez E, et al. Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genetics. 2008;4(8) Article ID e1000166.
    1. Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nature Reviews Immunology. 2008;8(10):776–787.
    1. Beutler B. Innate immunity: an overview. Molecular Immunology. 2004;40(12):845–859.
    1. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007;449(7164):819–826.
    1. Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA. A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection. Infection and Immunity. 2000;68(11):6398–6401.
    1. Sutherland AM, Walley KR, Russell JA. Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults. Critical Care Medicine. 2005;33(3):638–644.
    1. Chen KH, Gu W, Zeng L, et al. Identification of haplotype tag snps within the entire TLR2 gene and their clinical relevance in patients with major trauma. Shock. 2011;35(1):35–41.
    1. Chen K, Wang YT, Gu W, et al. Functional significance of the toll-like receptor 4 promoter gene polymorphisms in the Chinese Han population. Critical Care Medicine. 2010;38(5):1292–1299.
    1. Duan ZX, Gu W, Zhang LY, et al. Clinical relevance of the TLR4 11367 polymorphism in patients with major trauma. Archives of Surgery. 2009;144(12):1144–1148.
    1. Duan ZX, Zhu PF, Dong H, et al. Functional significance of the TLR4/11367 polymorphism identified in Chinese Han population. Shock. 2007;28(2):160–164.
    1. Gu W, Shan YA, Zhou J, et al. Functional significance of gene polymorphisms in the promoter of myeloid differentiation-2. Annals of Surgery. 2007;246(1):151–158.
    1. Gu W, Dong H, Jiang DP, et al. Functional significance of CD14 promoter polymorphisms and their clinical relevance in a Chinese Han population. Critical Care Medicine. 2008;36(8):2274–2280.
    1. Hubacek JA, Stüber F, Fröhlich D, et al. Gene variants of the bactericidal/permeability increasing protein and lipopolysaccharide binding protein in sepsis patients: gender-specific genetic predisposition to sepsis. Critical Care Medicine. 2001;29(3):557–561.
    1. Chien JW, Boeckh MJ, Hansen JA, Clark JG. Lipopolysaccharide binding protein promoter variants influence the risk for Gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation. Blood. 2008;111(4):2462–2469.
    1. Wurfel MM, Gordon AC, Holden TD, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. American Journal of Respiratory and Critical Care Medicine. 2008;178(7):710–720.
    1. Hawn TR, Misch EA, Dunstan SJ, et al. A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. European Journal of Immunology. 2007;37(8):2280–2289.
    1. Shalhub S, Junker CE, Imahara SD, Mindrinos MN, Dissanaike S, O’keefe GE. Variation in the TLR4 gene influences the risk of organ failure and shock posttrauma: a cohort study. Journal of Trauma. 2009;66(1):115–122.
    1. Feterowski C, Emmanuilidis K, Miethke T, et al. Effects of functional toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology. 2003;109(3):426–431.
    1. Jessen K, Lindboe S, Petersen A, Eugen-Olsen J, Benfield T. Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis. BMC Infectious Diseases. 2007;7, article no. 108
    1. Agnese DM, Calvano JE, Hahm SJ, et al. Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections. Journal of Infectious Diseases. 2002;186(10):1522–1525.
    1. Baier RJ, Loggins J, Yanamandra K. IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low birth weight infants. BMC Medicine. 2006;4, article no. 10
    1. de Aguiar BB, Girardi I, Paskulin DD, et al. CD14 expression in the first 24 h of sepsis: effect of -260C>T CD14 SNP. Immunological Investigations. 2008;37(8):752–769.
    1. D’Avila LC, Albarus MH, Franco CR, et al. Effect of CD14 -260C>T polymorphism on the mortality of critically ill patients. Immunology and Cell Biology. 2006;84(4):342–348.
    1. Hamann L, Kumpf O, Müller M, et al. A coding mutation within the first exon of the human MD-2 gene results in decreased lipopolysaccharide-induced signaling. Genes and Immunity. 2004;5(4):283–288.
    1. Medvedev AE, Lentschat A, Kuhns DB, et al. Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections. Journal of Experimental Medicine. 2003;198(4):521–531.
    1. Arcaroli J, Silva E, Maloney JP, et al. Variant IRAK-1 haplotype is associated with increased nuclear factor-κB activation and worse outcomes in sepsis. American Journal of Respiratory and Critical Care Medicine. 2006;173(12):1335–1341.
    1. Khor CC, Chapman SJ, Vannberg FO, et al. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nature Genetics. 2007;39(4):523–528.
    1. Chapman SJ, Khor CC, Vannberg FO, et al. IκB genetic polymorphisms and invasive pneumococcal disease. American Journal of Respiratory and Critical Care Medicine. 2007;176(2):181–187.
    1. Ma P, Chen D, Pan J, Du B. Genomic polymorphism within interleukin-1 family cytokines influences the outcome of septic patients. Critical Care Medicine. 2002;30(5):1046–1050.
    1. Wen AQ, Gu W, Wang J, et al. Clinical relevance of IL-1β promoter polymorphisms (-1470,-511, and-31) in patients with major trauma. Shock. 2010;33(6):576–582.
    1. Wen AIQ, Wang J, Feng K, Zhu PF, Jiang JX. Analysis of polymorphisms in the promoter region of interleukin-1β by restriction fragment length polymorphism-PCR. Chinese Journal of Traumatology. 2004;7(5):271–274.
    1. Read RC, Camp NJ, di Giovine FS, et al. An interleukin-1 genotype is associated with fatal outcome of meningococcal disease. Journal of Infectious Diseases. 2000;182(5):1557–1560.
    1. Arnalich F, López-Maderuelo D, Codoceo R, et al. Interleukin-1 receptor antagonist gene polymorphism and mortality in patients with severe sepsis. Clinical and Experimental Immunology. 2002;127(2):331–336.
    1. Vickers MA, Green FR, Terry C, et al. Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovascular Research. 2002;53(4):1029–1034.
    1. Tischendorf JJW, Yagmur E, Scholten D, et al. The interleukin-6 (IL6)-174 G/C promoter genotype is associated with the presence of septic shock and the ex vivo secretion of IL6. International Journal of Immunogenetics. 2007;34(6):413–418.
    1. Schlüter B, Raufhake C, Erren M, et al. Effect of the interleukin-6 promoter polymorphism (-174 G/C) on the incidence and outcome of sepsis. Critical Care Medicine. 2002;30(1):32–37.
    1. Gu W, Du DY, Huang J, et al. Identification of interleukin-6 promoter polymorphisms in the Chinese Han population and their functional significance. Critical Care Medicine. 2008;36(5):1437–1443.
    1. Wattanathum A, Manocha S, Groshaus H, Russell JA, Walley KR. Interleukin-10 haplotype associated with increased mortality in critically ill patients with sepsis from pneumonia but not in patients with extrapulmonary sepsis. Chest. 2005;128(3):1690–1698.
    1. Stanilova SA, Miteva LD, Karakolev ZT, Stefanov CS. Interleukin-10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility. Intensive Care Medicine. 2006;32(2):260–266.
    1. Shu Q, Fang X, Chen Q, Stuber F. IL-10 polymorphism is associated with increased incidence of severe sepsis. Chinese Medical Journal. 2003;116(11):1756–1759.
    1. Zeng L, Gu W, Chen K, et al. Clinical relevance of the interleukin 10 promoter polymorphisms in Chinese Han patients with major trauma: genetic association studies. Critical Care. 2009;13(6):p. R188.
    1. Gallagher PM, Lowe G, Fitzgerald T, et al. Association of IL-10 polymorphism with severity of illness in community acquired pneumonia. Thorax. 2003;58(2):154–156.
    1. Read RC, Teare DM, Pridmore AC, et al. The tumor necrosis factor polymorphism TNF (-308) is associated with susceptibility to meningococcal sepsis, but not with lethality. Critical Care Medicine. 2009;37(4):1237–1243.
    1. Azim K, McManus R, Brophy K, Ryan A, Kelleher D, Reynolds JV. Genetic polymorphisms and the risk of infection following esophagectomy. Positive association with TNF-α gene -308 genotype. Annals of Surgery. 2007;246(1):122–128.
    1. Barber RC, Aragaki CC, Rivera-Chavez FA, Purdue GF, Hunt JL, Horton JW. TLR4 and TNF-α polymorphisms are associated with an increased risk for severe sepsis following burn injury. Journal of Medical Genetics. 2004;41(11):808–813.
    1. Kovar FM, Marsik C, Cvitko T, Wagner OF, Jilma B, Endler G. The tumor necrosis factor α -308 G/A polymorphism does not influence inflammation and coagulation response in human endotoxemia. Shock. 2007;27(3):238–241.
    1. Gordon AC, Lagan AL, Aganna E, et al. TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study. Genes and Immunity. 2004;5(8):631–640.
    1. Nakada TA, Hirasawa H, Oda S, et al. Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients. Journal of Surgical Research. 2005;129(2):322–328.
    1. Shalhub S, Pham TN, Gibran NS, O’Keefe GE. Tumor necrosis factor gene variation and the bisk of mortality after burn injury: a cohort study. Journal of Burn Care and Research. 2009;30(1):105–111.
    1. Schueller AC, Heep A, Kattner E, et al. Prevalence of two tumor necrosis factor gene polymorphisms in premature infants with early onset sepsis. Biology of the Neonate. 2006;90(4):229–232.
    1. Mira JP, Cariou A, Grall F, et al. Association of TNF2, a TNF-α promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. Journal of the American Medical Association. 1999;282(6):561–568.
    1. Stassen NA, Leslie-Norfleet LA, Robertson AM, Eichenberger MR, Polk HC., Jr. Interferon-γ gene polymorphisms and the development of sepsis in patients with trauma. Surgery. 2002;132(2):289–292.
    1. Temple SEL, Cheong KY, Price P, Waterer GW. The microsatellite, macrophage migration inhibitory factor -794, may influence gene expression in human mononuclear cells stimulated with E. coli or S. pneumoniae. International Journal of Immunogenetics. 2008;35(4-5):309–316.
    1. Westendorp RGJ, Hottenga JJ, Slagboom PE. Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock. Lancet. 1999;354(9178):561–563.
    1. Kremer Hovinga JA, Franco RF, Zago MA, ten Cate H, Westendorp RGJ, Reitsma PH. A functional single nucleotide polymorphisms in the thrombin-activatable fibrinolysis inhibitor (TAFI) gene associates with outcome of meningococcal disease. Journal of Thrombosis and Haemostasis. 2004;2(1):54–57.
    1. Yan SB, Nelson DR. Effect of factor V Leiden polymorphism in severe sepsis and on treatment with recombinant human activated protein C. Critical care medicine. 2004;32(5):S239–S246.
    1. Manocha S, Russell JA, Sutherland AM, Wattanathum A, Walley KR. Fibrinogen-beta gene haplotype is associated with mortality in sepsis. Journal of Infection. 2007;54(6):572–577.
    1. Kovar FM, Marsik C, Jilma B, et al. The fibrinogen - 148 C/T polymorphism influences inflammatory response in experimental endotoxemia in vivo. Thrombosis Research. 2007;120(5):727–731.
    1. Gu W, Zeng L, Zhou J, et al. Clinical relevance of 13 cytokine gene polymorphisms in Chinese major trauma patients. Intensive Care Medicine. 2010;36(7):1261–1265.
    1. Levi M, de Jonge E, van der Poll T, ten Cate H. Disseminated intravascular coagulation. Thrombosis and Haemostasis. 1999;82(2):695–705.

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