Medicina genómica aplicada a la neumonía aguda comunitaria
Palabras clave:
NEUMONÍA, INFECCIONES COMUNITARIAS ADQUIRIDAS, GENOMICAResumen
Las infecciones del tracto respiratorio inferior constituyen un enorme flagelo para la humanidad. La neumonía aguda comunitaria es la principal enfermedad respiratoria por frecuencia y severidad. A pesar de los avances de la medicina moderna, su morbilidad y mortalidad permanecen prácticamente incambiadas.
La respuesta ante un agravio infeccioso es estrictamente individual al estar influida por la estructura genética del huésped.
La medicina genómica procura personalizar y optimizar el diagnóstico, pronóstico y tratamiento mediante el reconocimiento de la influencia que ejercen determinadas variantes genéticas, denominadas polimorfismos, en la susceptibilidad y evolución de las diversas patologías.
Los polimorfismos genéticos son capaces de modificar el riesgo de padecer determinado evento o suceso en una enfermedad específica por lo cual su reconocimiento permite personalizar la interacción entre ambiente y huésped.
En el presente artículo se describen los polimorfismos que están asociados positivamente con la evolución de la neumonía aguda comunitaria y qué aplicaciones clínicas podría tener la medicina genómica.
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(14) Waterer GW, Wunderink RG Genetic susceptibility to pneumonia. Clin Chest Med 2005; 26(1):29-38.
(15) Varmus H. Ten Years on- the human genome and medicine. N Engl J Med 2010; 362(21):2028-9.
(16) Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science 2001; 291(5507):1304-51.
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(19) International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature 2007; 449(7164):851-61.
(20) Attia J, Ioannidis JP, Thakkinstian A, McEvoy M, Scott RJ, Minelli C, et al. How to use an article about genetic association. A: background Concepts. JAMA 2009; 301(1):74-81.
(21) Turner MW. Mannose-binding lectin (MBL) in health and disease. Immunobiology 1998; 199(2):327-39.
(22) Sastry K, Herman GA, Day L, Deignan E, Bruns G, Morton CC, et al. The human mannose-binding protein gene: exon structure reveals its evolutionary relationship to a human pulmonary surfactant gene and localization to chromosome 10. J Exp Med 1989; 170(4):1175-89.
(23) Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP, et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 1995; 155(6):3013-20.
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(25) García-Laorden MI, Solé-Violán J, Rodríguez de Castro F, Aspa J, Briones ML, et al. Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults. J Allergy Clin Immunol 2008; 122(2):368-74.
(26) Boeken U, Feindt P, Zimmermann N, Kalweit G, Petzold T, Gams E. Increased preoperative C-reactive protein (CRP)-values without signs of an infection and complicated course after cardiopulmonary bypass (CPB)-operations. Eur J Cardiothorac Surg 1998; 13(5):541-5.
(27) Mätzke S, Biancari F, Ihlberg L, Albäck A, Kantonen I, Railo M, et al. Increased preoperative C-reactive protein level as a prognostic factor for postoperative amputation after femoropopliteal bypass surgery for CLI. Ann Chir Gynaecol 2001; 90(1):19-22.
(28) Póvoa P, Almeida E, Moreira P, Fernandes A, Mealha R, Aragão A, et al. C-reactive protein as an indicator of sepsis. Intensive Care Med 1998; 24(10):1052-6.
(29) Mukamal KJ, Pai JK, O'Meara ES, Tracy RP, Psaty BM, Kuller LH, et al. CRP gene variation and risk of community-acquired pneumonia. Respirology 2010; 15(1):160-4.
(30) van Sorge NM, van der Pol WL, van de Winkel JG. FcgammaR polymorphisms: Implications for function, disease susceptibility and immunotherapy. Tissue Antigens 2003; 61(3):189-202.
(31) Sanders LA, Feldman RG, Voorhorst-Ogink MM, de Haas M, Rijkers GT, Capel PJ, et al. Human immunoglobulin G (IgG) Fc receptor IIA (CD32) polymorphism and IgG2-mediated bacterial phagocytosis by neutrophils. Infect Immun 1995; 63(1):73-81.
(32) Parren PW, Warmerdam PA, Boeije LC, Arts J, Westerdaal NA, Vlug A, et al. On the interaction of IgG subclasses with the low affinity FcgammaRIIa (CD32) on human monocytes, neutrophils, and platelets: analysis of a functional polymorphism to human IgG2. J Clin Investig 1992; 90(4):1537-46.
(33) Yee AM, Phan HM, Zuniga R, Salmon JE, Musher DM. Association between FcgammaRIIa-R131 allotype and bacteremic pneumococcal pneumonia. Clin Infect Dis 2000; 30(1):25-8.
(34) Endeman H, Cornips MC, Grutters JC, van den Bosch JM, Ruven HJ, van Velzen-Blad H, et al. The Fcgamma receptor IIA-R/R131 genotype is associated with severe sepsis in community-acquired pneumonia. Clin Vaccine Immunol 2009; 16(7):1087-90.
(35) Waterer GW, Quasney MW, Cantor RM, Wunderink RG. Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations. Am J Respir Crit Care Med 2001; 163(7):1599-604.
(36) Schaaf B, Rupp J, Muller-Steinhardt M, Kruse J, Boehmke F, Maass M, et al. The interleukin-6 -174 promoter polymorphism is associated with extrapulmonary bacterial dissemination in Streptococcus pneumonia infection. Cytokine 2005; 31(4):324-8.
(37) Solé-Violán J, de Castro F, García-Laorden MI, Blanquer J, Aspa J, Borderías L, et al. Genetic variability in the severity and outcome of community-acquired pneumonia. Respir Med 2010; 104(3):440-7.
(38) Oberholzer A, Oberholzer C, Moldawer LL. Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med 2002; 30(1Suppl):S58-S63.
(39) 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(7):407-13.
(40) Westendorp RG, Langermans JA, Huizinga TW, Elouali AH, Verweij CL, Boomsma DI, et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet 1997; 349(9046):170-3.
(41) Gallagher PM, Lowe G, Fitzgerald T, Bella A, Greene CM, McElvaney NG, et al. Association of IL-10 polymorphism with severity of illness in community acquired pneumonia. Thorax 2003; 58(2):154-6.
(42) Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24(1):1-8.
(43) Galley HF, Lowe PR, Carmichael RL, Webster NR. Genotype and interleukin-10 responses after cardiopulmonary bypass. Br J Anaesth 2003; 91(3): 424-6.
(44) Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 2003; 3(10):791-800.
(45) Cohen J, Guyatt G, Bernard GR, Calandra T, Cook D, Elbourne D, et al. New strategies for clinical trials in patients with sepsis and septic shock. Crit Care Med 2001; 29(4):880-6.
(46) Lehmann LE, Novender U, Schroeder S, Pietsch T, von Spiegel T, Putensen C, et al. Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis. Intensive Care Med 2001; 27(8):1412-5.
(47) Bozza FA, Gomes RN, Japiassú AM, Soares M, Castro-Faria-Neto HC, Bozza PT, et al. Macrophage migration inhibitory factor levels correlate with fatal outcome in sepsis. Shock 2004; 22(4):309-13.
(48) Gando S, Nishihira J, Kobayashi S, Morimoto Y, Nanzaki S, Kemmotsu O. Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome. Intensive Care Med 2001; 27(7):1187-93.
(49) Yende S, Angus DC, Kong L, Kellum JA, Weissfeld L, Ferrell R, et al. The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia. FASEB J 2009; 23(8):2403-11.
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2011-04-30
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1.
Cardinal P, Rieppi G, Bengochea M. Medicina genómica aplicada a la neumonía aguda comunitaria. Rev. Méd. Urug. [Internet]. 30 de abril de 2011 [citado 26 de diciembre de 2024];27(1):42-9. Disponible en: https://revista.rmu.org.uy/index.php/rmu/article/view/405
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