Subscribe to RSS
DOI: 10.1055/s-2006-948292
Genomics of Acute Lung Injury
Publication History
Publication Date:
14 August 2006 (online)
ABSTRACT
Acute lung injury (ALI) is a complex syndrome involving the interplay of both environmental (such as the addition of mechanical ventilation) and genetic factors. Clinical models have identified risk factors for development and poor outcome but these strategies remain imprecise. To better understand the mechanisms of pathogenesis associated with mechanisms of ALI, candidate genes identified by global expression profiling or related literature searches are being explored for relevant polymorphisms (single base pair substitutions) that can affect both ALI susceptibility and outcome. This article summarizes several specific genetic association studies that have been conducted in ALI and reviews supporting data from in vitro and in vivo models of the disease and clinical observations. Although valuable information has been reported to date, intense analyses are needed in this developing discipline to assure significant clinical utility. The detailing of specific associated polymorphisms will continue to provide new insights in the understanding of disease pathogenesis, and promise to reveal novel molecular targets and personalized treatments to prevent the disease.
KEYWORDS
Case-control association study - SNP - conserved expression patterns
REFERENCES
- 1 Rubenfeld G D, Caldwell E, Peabody E et al.. Incidence and outcomes of acute lung injury. N Engl J Med. 2005; 353 1685-1693
- 2 Ware L B, Matthay M A. The acute respiratory distress syndrome. N Engl J Med. 2000; 342 1334-1349
- 3 Moss M, Mannino D M. Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979-1996). Crit Care Med. 2002; 30 1679-1685
- 4 Kleeberger S R, Peden D. Gene-environment interactions in asthma and other respiratory diseases. Annu Rev Med. 2005; 56 383-400
- 5 Grigoryev D N, Ma S F, Irizarry R A, Ye S Q, Quackenbush J, Garcia J G. Orthologous gene-expression profiling in multi-species models: search for candidate genes. Genome Biol. 2004; 5 R34
- 6 Ma S F, Grigoryev D N, Taylor A D et al.. Bioinformatic identification of novel early stress response genes in rodent models of lung injury. Am J Physiol Lung Cell Mol Physiol. 2005; 289 L468-L477
- 7 Grigoryev D N, Finigan J H, Hassoun P, Garcia J G. Science review: searching for gene candidates in acute lung injury. Crit Care. 2004; 8 440-447
- 8 Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990; 86 1343-1346
- 9 Tiret L, Rigat B, Visvikis S et al.. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992; 51 197-205
- 10 Suehiro T, Morita T, Inoue M, Kumon Y, Ikeda Y, Hashimoto K. Increased amount of the angiotensin-converting enzyme (ACE) mRNA originating from the ACE allele with deletion. Hum Genet. 2004; 115 91-96
- 11 Marshall R P, Webb S, Bellingan G J et al.. Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002; 166 646-650
- 12 Jerng J S, Yu C J, Wang H C, Chen K Y, Cheng S L, Yang P C. Polymorphism of the angiotensin-converting enzyme gene affects the outcome of acute respiratory distress syndrome. Crit Care Med. 2006; 34 1001-1006
- 13 Imai Y, Kuba K, Rao S et al.. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005; 436 112-116
- 14 Chiu R W, Tang N L, Hui D S et al.. ACE2 gene polymorphisms do not affect outcome of severe acute respiratory syndrome. Clin Chem. 2004; 50 1683-1686
- 15 Chan K C, Tang N L, Hui D S et al.. Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study. BMC Infect Dis. 2005; 5 26
- 16 Marshall R P, Webb S, Hill M R, Humphries S E, Laurent G J. Genetic polymorphisms associated with susceptibility and outcome in ARDS. Chest. 2002; 121 68S-69S
- 17 Holub M, Lawrence D A. Influence of endotoxin-induced acute lung injury on pulmonary innate and adaptive immunity. APMIS. 2003; 111 571-580
- 18 Hollegaard M V, Bidwell J L. Cytokine gene polymorphism in human disease: on-line databases, supplement 3. Genes Immun. 2006; , In press
- 19 Fishman D, Faulds G, Jeffery R et al.. 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. 1998; 102 1369-1376
- 20 Jerrard-Dunne P, Sitzer M, Risley P et al.. Interleukin-6 promoter polymorphism modulates the effects of heavy alcohol consumption on early carotid artery atherosclerosis: the Carotid Atherosclerosis Progression Study (CAPS). Stroke. 2003; 34 402-407
- 21 Endler G, Marsik C, Joukhadar C et al.. The interleukin-6 G(- 174)C promoter polymorphism does not determine plasma interleukin-6 concentrations in experimental endotoxemia in humans. Clin Chem. 2004; 50 195-200
- 22 Sutherland A M, Walley K R, Manocha S, Russell J A. The association of interleukin 6 haplotype clades with mortality in critically ill adults. Arch Intern Med. 2005; 165 75-82
- 23 Kitamura A, Hasegawa G, Obayashi H et al.. Interleukin-6 polymorphism (- 634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes. Diabet Med. 2002; 19 1000-1005
- 24 Terry C F, Loukaci V, Green F R. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000; 275 18138-18144
- 25 Fife M S, Ogilvie E M, Kelberman D et al.. Novel IL-6 haplotypes and disease association. Genes Immun. 2005; 6 367-370
- 26 Marchant A, Deviere J, Byl B, De Groote D, Vincent J L, Goldman M. Interleukin-10 production during septicaemia. Lancet. 1994; 343 707-708
- 27 Neidhardt R, Keel M, Steckholzer U et al.. Relationship of interleukin-10 plasma levels to severity of injury and clinical outcome in injured patients. J Trauma. 1997; 42 863-870
- 28 Monneret G, Finck M E, Venet F et al.. The anti-inflammatory response dominates after septic shock: association of low monocyte HLA-DR expression and high interleukin-10 concentration. Immunol Lett. 2004; 95 193-198
- 29 Westendorp R G, Langermans J A, Huizinga T W et al.. Genetic influence on cytokine production and fatal meningococcal disease. Lancet. 1997; 349 170-173
- 30 Reuss E, Fimmers R, Kruger A, Becker C, Rittner C, Hohler T. Differential regulation of interleukin-10 production by genetic and environmental factors: a twin study. Genes Immun. 2002; 3 407-413
- 31 Eskdale J, Keijsers V, Huizinga T, Gallagher G. Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus. Genes Immun. 1999; 1 151-155
- 32 Kube D, Rieth H, Eskdale J, Kremsner P G, Gallagher G. Structural characterisation of the distal 5′ flanking region of the human interleukin-10 gene. Genes Immun. 2001; 2 181-190
- 33 Suarez A, Castro P, Alonso R, Mozo L, Gutierrez C. Interindividual variations in constitutive interleukin-10 messenger RNA and protein levels and their association with genetic polymorphisms. Transplantation. 2003; 75 711-717
- 34 Turner D M, Williams D M, Sankaran D, Lazarus M, Sinnott P J, Hutchinson I V. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997; 24 1-8
- 35 Koss K, Satsangi J, Fanning G C, Welsh K I, Jewell D P. Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. Genes Immun. 2000; 1 185-190
- 36 Kurreeman F A, Schonkeren J J, Heijmans B T, Toes R E, Huizinga T W. Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level. Hum Mol Genet. 2004; 13 1755-1762
- 37 Mormann M, Rieth H, Hua T D et al.. Mosaics of gene variations in the interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. Genes Immun. 2004; 5 246-255
- 38 Schippers E F, van 't Veer C, van Voorden S et al.. IL-10 and Toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin. Cytokine. 2005; 29 215-228
- 39 Gong M N, Thompson B T, Williams P L et al.. Interleukin-10 polymorphism in position - 1082 and acute respiratory distress syndrome. Eur Respir J. 2006; 27 674-681
- 40 Latifi S Q, O'Riordan M A, Levine A D. Interleukin-10 controls the onset of irreversible septic shock. Infect Immun. 2002; 70 4441-4446
- 41 Dudek S M, Garcia J G. Cytoskeletal regulation of pulmonary vascular permeability. J Appl Physiol. 2001; 91 1487-1500
- 42 Wainwright M S, Rossi J, Schavocky J et al.. Protein kinase involved in lung injury susceptibility: evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment. Proc Natl Acad Sci USA. 2003; 100 6233-6238
- 43 Eutamene H, Theodorou V, Schmidlin F et al.. LPS-induced lung inflammation is linked to increased epithelial permeability: role of MLCK. Eur Respir J. 2005; 25 789-796
- 44 Gao L, Grant A, Halder I et al.. Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Am J Respir Cell Mol Biol. 2006; 34 487-495
- 45 Nemeth E, Tashima L S, Yu Z, Bryant-Greenwood G D. Fetal membrane distention, I: Differentially expressed genes regulated by acute distention in amniotic epithelial (WISH) cells. Am J Obstet Gynecol. 2000; 182 50-59
- 46 Ognjanovic S, Bao S, Yamamoto S Y, Garibay-Tupas J, Samal B, Bryant-Greenwood G D. Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes. J Mol Endocrinol. 2001; 26 107-117
- 47 Ye S Q, Simon B A, Maloney J P et al.. Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. Am J Respir Crit Care Med. 2005; 171 361-370
- 48 Ye S Q, Zhang L Q, Adyshev D et al.. Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvasc Res. 2005; 70 142-151
- 49 Pan T, Nielsen L D, Allen M J et al.. Serum SP-D is a marker of lung injury in rats. Am J Physiol Lung Cell Mol Physiol. 2002; 282 L824-L832
- 50 Ingenito E P, Mora R, Cullivan M et al.. Decreased surfactant protein-B expression and surfactant dysfunction in a murine model of acute lung injury. Am J Respir Cell Mol Biol. 2001; 25 35-44
- 51 Eisner M D, Parsons P, Matthay M A, Ware L, Greene K. Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury. Thorax. 2003; 58 983-988
- 52 Lin Z, Pearson C, Chinchilli V et al.. Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. Clin Genet. 2000; 58 181-191
- 53 Gong M N, Wei Z, Xu L L, Miller D P, Thompson B T, Christiani D C. Polymorphism in the surfactant protein-B gene, gender, and the risk of direct pulmonary injury and ARDS. Chest. 2004; 125 203-211
- 54 Quasney M W, Waterer G W, Dahmer M K et al.. Association between surfactant protein B + 1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia. Crit Care Med. 2004; 32 1115-1119
- 55 Seybold J, Thomas D, Witzenrath M et al.. Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability. Blood. 2005; 105 3569-3576
- 56 Parsons P E, Matthay M A, Ware L B, Eisner M D. Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2005; 288 L426-L431
- 57 Meduri G U, Headley S, Kohler G et al.. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS: plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest. 1995; 107 1062-1073
- 58 Hajeer A H, Hutchinson I V. Influence of TNFalpha gene polymorphisms on TNFalpha production and disease. Hum Immunol. 2001; 62 1191-1199
- 59 Knight J C, Keating B J, Rockett K A, Kwiatkowski D P. In vivo characterization of regulatory polymorphisms by allele-specific quantification of RNA polymerase loading. Nat Genet. 2003; 33 469-475
- 60 Gong M N, Zhou W, Williams P L et al.. - 308GA and TNFB polymorphisms in acute respiratory distress syndrome. Eur Respir J. 2005; 26 382-389
- 61 Dvorak H F, Brown L F, Detmar M, Dvorak A M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995; 146 1029-1039
- 62 Thickett D R, Armstrong L, Millar A B. A role for vascular endothelial growth factor in acute and resolving lung injury. Am J Respir Crit Care Med. 2002; 166 1332-1337
- 63 Medford A R, Keen L J, Bidwell J L, Millar A B. Vascular endothelial growth factor gene polymorphism and acute respiratory distress syndrome. Thorax. 2005; 60 244-248
- 64 Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E. A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res. 2000; 37 443-448
- 65 Villar J, Maca-Meyer N, Perez-Mendez L, Flores C. Bench-to-bedside review: understanding genetic predisposition to sepsis. Crit Care. 2004; 8 180-189
Joe G.N GarciaM.D.
Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago
5841 S. Maryland Ave., W604, Chicago, IL 60637
Email: jgarcia@medicine.bsd.uchicago.edu