Epigenética en el asma. Lo esencial

Miguel Perpiñá Tordera

Resumen


El asma es una entidad compleja donde aparecen implicados genes y entorno y en la que mecanismos epigenéticos pueden mediar parte de los efectos que ejercen los factores ambientales sobre la historia natural de dicha enfermedad. La epigenética describe los cambios en la expresión génica, heredables durante la mitosis y meiosis, potencialmente reversibles y que no entrañan una corrección en la secuencia del ácido desoxiribonucléico (ADN). Incluyen, entre otros, la metilación o desmetilación del ADN, la acetilación/deacetilación de las histonas y los cambios inducidos por los micro ARNs que son una clase de ácido ribonucléico no codificante, evolutivamente conservados y de pequeño tamaño. La presente revisión  focaliza sus comentarios en un aspecto muy concreto pero de gran atractivo a la luz de las investigaciones relacionadas con el orígen temprano de las enfermedades crónicas: el análisis de cómo determinadas circunstancias presentes en el hábitat que nos rodea (particularmente alérgenos, tabaco e ingesta de ácido fólico) modulan la activación de ciertos genes favoreciendo así el desarrollo del proceso respiratorio durante las primeras etapas de la vida. No obstante, y a pesar de su relevancia teórica, la interpretación final de la información disponible resulta todavía equívoca dado que no siempre es posible fijar si las alteraciónes descritas son causa o consecuencia de la enfermedad en cuestión. En cualquier caso, el análisis de tales mecanismos constituye un campo de investigación novedoso cuyos resultados a buen seguro incrementarán el conocimiento general acerca de las variaciones del epigenoma y, cara a la práctica, susceptibles de ser utilizados en las estrategias terapéuticas relacionadas con esta patología y su prevención. 


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Referencias


Rice JP, Saccone NL, Rasmussen E. Definition of the phenotype. Adv Genet. 2001;42:69–76.

Hunter DJ. Gene-environment interactions in human diseases. Nat Rev Genet. 2005;6:287–98.

Carey JC, Borde LB, Bamshad MJ. Genética médica (IV edición). Barcelona, Elsevier. 2011.

International human genome sequencing consortium. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.

Vercelli D. Genetics, epigenetics, and the environment: switching, buffering, releasing. J Allergy Clin Immunol. 2004;113:381–6.

Felsenfeld G. A brief history of epigenetics. Cold Spring Harb Perspect Biol. 2014;6:a018200.

Petronis A. Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature. 2010;465:721–7.

Renz H, Von Mutius E, Brandtzaeg P, Cookson WO, Autenrieth IB, Haller D. Gene-environment interactions in chronic inflammatory disease. Nat Immunol. 2011;12:273–7.

Seibold MA, Schwartz DA. The lung: the natural boundary between nature and nurture. Annu Rev Physiol. 2011;73:457–78.

Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol. 2008;8:169–82.

March ME, Sleiman PM, Hakornarson H. The genetics of asthma and allergic disorders. Discov Med. 2011;11:35–45.

Thomsen SF. Genetics of asthma: an introduction for the clinician. Eur Clin Respir J. 2015;2:10.3402/ecrj.v2.24643.

Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med. 2002;166:392–6.

Cosío BG, Mann B, Ito K, Jazrawi E, Barnes PJ, Adcock IM. Histone acetylase and deacetylase activity in alveolar macrophages and blood monocytes in asthma. Am J Respir Crit Care Med. 2004;170:141–7.

Gruzieva O, Merid SK, Melén E. An update on epigenetics and childhood respiratory diseases. Paediatr Respir Rev. 2014;15:348–54.

Gunawardhana LP, Gibson PG, Simpson JL, Benton MC, Lea RA, Baines KJ. Characteristic DNA methylation profiles in peripheral blood monocytes are associated with inflammatory phenotypes of asthma. Epigenetics. 2014;9:1302–16.

Barnes PJ. Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2009;6:693–6.

Zhang H, Tong X, Holloway JW, Rezwan FI, Lockett GA, Patil V, et al. The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition. Clin Epigenetics. 2014;6:8.

Vercelli D. Does epigenetics play a role in human asthma? Allergol Int. 2016;65:123–6.

Perry MM, Baker JE, Gibeon DS, Adcock IM, Chung KF. Airway smooth muscle hyperproliferation is regulated by microRNA-221 in severe asthma. Am J Respir Cell Mol Biol. 2014;50:7–17.

Ho SM. Environmental epigenetics of asthma: an update. J Allergy Clin Immunol. 2010;126:453–65.

Gluckman PD, Hanson MA, Buklijas T. A conceptual framework for the developmental origins of health and disease. J Dev Orig Health Dis. 2010;1:6–18.

Krauss-Etschmann S, Bush A, Bellusci S, Brusselle GG, Dahlén SE, Dehmel S, et al. Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung diseases. Thorax. 2013;68:380–4.

Bousquet J, Antó JM, Berkouk K, Gergen P, Antunes JP, Augé P, et al. Developmental determinants in non-communicable chronic diseases and ageing. Thorax. 2015;70:595–7.

Waddington CH. An introduction to modern genetics. New York, Macmillan. 1939.

Holliday R. Epigenetics comes of age in the twenty first century. J Genet. 2002;81:1–4.

Bird A. Perceptions of epigenetics. Nature. 2007;447:396–8.

Tost J. Epigenetics. Norwitch, Horizon Scientific Press. 2008.

Auclair G, Weber M. Mechanisms of DNA methylation and demethylation in mammals. Biochimie. 2012;94:2202–11.

Du Q, Luu PL, Stirzaker C, Clark SJ. Methyl-CpG-binding domain proteins: readers of the epigenome. Epigenomics. 2015;7:1051–73.

Rice JC, Allis CD. Code of silence. Nature. 2001;414:

–61.

Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–95.

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

Ender C, Meister G. Argonaute proteins at a glance. J Cell Sci. 2010;123:1819–23.

Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9:102–14.

Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. 2012;22:125–32.

Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.

Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146:353–8.

Barker DJ, Osmond C. Infant mortality, childhood nutrition and ischaemic heart disease in England and Wales. Lancet. 1986;1:1077–81.

Barker DJ, Osmond C. Diet and coronary heart disease in England and Wales during and after the Second World War. J Epidemiol Community Health. 1986;40:37–44.

Neel JV. Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet. 1962;14:353–62.

Roseboom T, De Rooij S, Painter R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006;82:485–91.

Roseboom TJ, Painter RC, Van Abeelen AFM, Veenendaal MV, De Rooij SR. Hungry in the womb: What are the consequences? Lessons from the Dutch famine. Maturitas. 2011;70:141–5.

Bygren LO, Kaati G, Edvinsson S. Longevity determined by paternal ancestors’ nutrition during their slow growth period. Acta Biotheor. 2001;49:53–9.

Hanson MA, Gluckman PD. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev. 2014;94:1027–76.

Harb H, Renz H. Update on epigenetics in allergic disease. J Allergy Clin Immunol. 2015;135:15–24.

Brand S, Kesper DA, Teich R, Kilic-Niebergall, Pinkenburg O, Bothur E, et al. DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma. J Allergy Clin Immunol. 2012;129:1602–10.

Pascual M, Suzuki M, Isidoro-García M, Padrón J, Turner T, Lorente F, et al. Epigenetic changes in B lymphocytes associated with house dust mite allergic asthma. Epigenetics. 2011;6:1131–7.

Shang Y, Das S, Rabold R, Sham JS, Mitzner W, Tang WY. Epigenetic alterations by DNA methylation in house dust mite-induced airway hyperresponsiveness. Am J Respir Cell Mol Biol. 2013;49:279–87.

Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005;127:1232–41.

Magnus MC, Håberg SE, Karlstad Ø, Nafstad P, London SJ, Nystad W. Grandmother’s smoking when pregnant with the mother and asthma in the grandchild: the Norwegian Mother and Child Cohort Study. Thorax. 2015;70:237–43.

Klingbeil EC, Hew KM, Nygaard UC, Nadeau KC. Polycyclic aromatic hydrocarbons, tobacco smoke, and epigenetic remodeling in asthma. Immunol Res. 2014;58:369–73.

Markunas CA, Xu Z, Harlid S, Wade PA, Lie RT, Taylor JA, et al. Identification of DNA methylation changes in newborns related to maternal smoking during pregnancy. Environ Health Perspect. 2014;122:1147–53.

Herberth G, Bauer M, Gasch M, Hinz D, Röder S, Olek S, et al.; Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk study group. Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers. J Allergy Clin Immunol. 2014;133:543–50.

Wang IJ, Chen SL, Lu TP, Chuang EY, Chen PC. Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis. Clin Exp Allergy. 2013;43:535–43.

Liu YJ. Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med. 2006;203:269–73.

Shorter KR, Anderson V, Cakora P, Owen A, Lo K, Crossland J, et al. Pleiotropic effects of a methyl donor diet in a novel animal model. PLoS One. 2014;9:e104942.

Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li Z, Tomfohr J, et al. In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest. 2008;118:3462–9.

Håberg SE, London SJ, Stigum H, Nafstad P, Nystad W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child. 2009;94:180–4.

Whitrow MJ, Moore VM, Rumbold AR, Davies MJ. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol. 2009;170:1486–93.

Amarasekera M, Martino D, Ashley S, Harb H, Kesper D, Strickland D, et al. Genome-wide DNA methylation profiling identifies a folate-sensitive region of differential methylation upstream of ZFP57-imprinting regulator in humans. FASEB J. 2014;20:4068–76.


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