Epigenetic regulation: The interface between prenatal and early-life exposure and asthma susceptibility

Environmental and Molecular Mutagenesis

Volumn 55, Issue 3, 2014, Pages 231-243

  De Planell Saguer, Mariàngels ^a   Lovinsky Desir, Stephanie ^a   Miller, Rachel L ^a,b  

^a Columbia University College of Physicians and Surgeons ^*  (United States)

^b NONE   (United States)

Author keywords

Asthma; Environment; Epigenetic regulation; Precision medicine; Prenatal exposures

Indexed keywords

ALLERGEN; ARGINASE; BIOLOGICAL MARKER; DIESEL FUEL; ENVIRONMENTAL TOBACCO SMOKE; METHYL GROUP; NITRIC OXIDE SYNTHASE; POLYCYCLIC AROMATIC HYDROCARBON; TOBACCO SMOKE; UNCLASSIFIED DRUG; VOLATILE ORGANIC COMPOUND;

ALLERGY; ANTIGEN PRESENTATION; ASTHMA; CELL DIFFERENTIATION; DENDRITIC CELL; DIET SUPPLEMENTATION; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; ECOSYSTEM RESTORATION; ENVIRONMENTAL EXPOSURE; EPIGENETICS; EXHAUST GAS; HELPER CELL; IMMUNE RESPONSE; MEDICAL RESEARCH; MICROORGANISM; PARTICULATE MATTER; PHENOTYPIC PLASTICITY; PRENATAL EXPOSURE; REVIEW; RISK ASSESSMENT; SIGNAL TRANSDUCTION; TH17 CELL; TREATMENT OUTCOME;

ASTHMA; ENVIRONMENT; EPIGENETIC REGULATION; PRECISION MEDICINE; PRENATAL EXPOSURES;

ADOLESCENT; ANTIGEN PRESENTATION; ASTHMA; BIOLOGICAL MARKERS; CHILD; CHILD, PRESCHOOL; DENDRITIC CELLS; ENVIRONMENTAL EXPOSURE; EPIGENESIS, GENETIC; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENETIC PREDISPOSITION TO DISEASE; HUMANS; HYPERSENSITIVITY; MALE; MATERNAL EXPOSURE; PARTICULATE MATTER; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY; VOLATILE ORGANIC COMPOUNDS;

EID: 84896728995     PISSN: 08936692     EISSN: 10982280     Source Type: Journal    
DOI: 10.1002/em.21836     Document Type: Review

References (119)

1. Abdulamir AS, Hafidh RR, Abubakar F, Abbas KA. 2008. Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma. BMC Immunol 9:73.
2. Arshad S, Karmaus W, Raza A, Kurukulaaratchy R, Matthews S, Holloway J, Sadeghnejad A, Zhang H, Roberts G, Ewart SL. 2012. The effect of parental allergy on childhood allergic diseases depends on the sex of the child. J Allergy Clin Immunol 130:427-434.
3. Asher MI. 2011. Urbanisation, asthma and allergies. Thorax 66:1025-1026.
4. Avni O, Lee D, Macian F, Szabo SJ, Glimcher LH, Rao A. 2002. T(H) cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes. Nat Immunol 3:643-651.
5. Baccarelli A, Rusconi F, Bollati V, Catelan D, Accetta G, Hou L, Barbone F, Bertazzi PA, Biggeri A. 2012. Nasal cell DNA methylation, inflammation, lung function and wheezing in children with asthma. Epigenomics 4:91-100.
6. Barnes PJ. 2009. Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 6:693-696.
7. Bell ML, Ebisu K, Peng RD, Samet JM, Dominici F. 2009. Hospital admissions and chemical composition of fine particle air pollution. Am J Respir Crit Care Med 179:1115-1120.
8. Benetti R, Gonzalo S, Jaco I, Muñoz P, Gonzalez S, Schoeftner S, Murchinson E, Andl T, Chen T, Klatt P, et al. 2008. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol 15:268-279.
9. Benson RC, Hardy KA, Morris, CR. 2011. Arginase and arginine dysregulation in asthma. J Allergy 736319.
10. Blümer N, Sel S, Virna S, Patrascan C, Zimmermann S, Herz U, Renz H, Garn H. 2007. Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring. Clin Exp Allergy 37:348-357.
11. Brand S, Kesper DA, Teich R, Kilic-Niebergall E, Pinkenburg O, Bothur E, Lohoff M, Garn H, Pfefferle PI, Renz H. 2012. DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma. J Allergy Clin Immunol 129:1602-1610.
12. Breitling LP, Yang R, Korn B, Burwinkel B, Brenner H. 2011. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am J Human Genet 88:450-457.
13. Breton CV, Byun HM, Wang X, Salam MT, Siegmund K, Gilliland FD. 2011. DNA methylation in the arginase-nitric oxide synthase pathway is associated with exhaled nitric oxide in children with asthma. Am J Respir Crit Care Med 184:191-197.
14. Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. 2009. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med 180:462-467.
15. Calderon C, Rivera L, Hutchinson P, Dagher H, Villanueva E, Ghildyal R, Bardin PG, Freezer NJ. 2009. T-cell cytokine profiles are altered in childhood asthma exacerbation. Respirology 14:264-269.
16. Carmines E, Gaworski C, Faqi A, Rajendran N. 2003. In utero exposure to 1R4F reference cigarette smoke: evaluation of developmental toxicity. Toxicol Sci 75:134-147.
17. Chatzi L, Torrent M, Romieu I, Garcia-Esteban R, Ferrer C, Vioque J, Kogevinas M, Sunyer J. 2008. Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood. Thorax 63:507-513.
18. Cheung P, Lau P. 2005. Epigenetic regulation by histone methylation and histone variants. Mol Endocrinol 19:563-573.
19. Collison A, Mattes J, Plank M, Foster PS. 2011. Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy Clin Immunol 128:160-167.
20. Cookson WO, Young RP, Sandford AJ, Moffatt MF, Shirakawa T, Sharp PA, Faux JA, Le Souf PN, Julier C, Lathrop GM, et al. 1992. Maternal inheritance of atopic IgE responsiveness on chromosome 11q. Lancet 340:381-384.
21. Cornell AG, Chillrud SN, Mellins RB, Acosta LM, Miller RL, Quinn JW, Yan B, Divjan A, Olmedo OE, Lopez-Pintado S, et al. 2012. Domestic airborne black carbon and exhaled nitric oxide in children in NYC. J Exp Sci Environ Epidemiol 22:258-266.
22. Cosío BJ, Mann B, Ito K, Jazrawi E, Barnes PJ, Chung KF, Adcock IM. 2004. Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma. Am J Respir Crit Care Med 170:141-147.
23. De Marco R, Pattaro C, Locatelli F, Svanes C. 2004. Influence of early life exposures on incidence and remission of asthma throughout life. J Allergy Clin Immunol 113:845-852.
24. Dong J, Chang HD, Ivascu C, Qian Y, Rezai S, Okhrimenko A, Cosmi L, Maggi L, Eckhardt F, Wu P, et al. 2013. Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-gamma memory in human CD4(+) T lymphocytes. Eur J Immunol 43:793-804.
25. Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL. 2003. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol 112:1178-1184.
26. Dweik RA, Sorkness RL, Wenzel S, Hammel J, Curran-Everett D, Comhair S, Bleecker E, Busse W, Calhoun WJ, Castro M, et al. 2010. Use of exhaled nitric oxide measurement to identify a reactive, at risk phenotype among patients with asthma. Am J Respir Crit Care Med 181:1033-1041.
27. Ehlers M, Laule-Kilian K, Petter M, Aldrian CJ, Grueter B, Wurch A, Yoshida N, Watanabe T, Satake M, Steimle V. 2003. Morpholino antisense oligonucleotide-mediated gene knockdown during thymocyte development reveals role for Runx3 transcription factor in CD4 silencing during development of CD4-/CD8+ thymocytes. J Immunol 171:3594-3604.
28. Fedulov AV, Kobzik L. 2011. Allergy risk is mediated by dendritic cells with congenital epigenetic changes. Am J Respir Cell Mol Biol 44:285-292.
29. Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG. 2006. Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide. J Allergy Clin Immunol 118:1218-1225.
30. Floess S, Freyer J, Siewert C, Baron U, Olek S, Polansky J, Schlawe K, Chang HD, Bopp T, Schmitt E, et al. 2007. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol 5:e38.
31. Fraga M, Ballestar E, Paz M, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Ciqudosa JC, Urioste M, Benitez J, et al. 2005. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604-10609.
32. Fuks F. 2005. DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev 15:490-495.
33. Gao A, Zuo X, Liu Q, Lu X, Guo W, Tian L. 2010. Methylation of PARP-1 promoter involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression. Toxicol Lett 195:114-118.
34. Gilliland F, Li Y, Dubeau L, Berhane K, Avol E, McConnell R, Gauderman WJ, Peters JM. 2002. Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med 166:457-463.
35. Håberg S, London S, Nafstad P, Nilsen R, Ueland P, Vollset S, Nystad W. 2011. Maternal folate levels in pregnancy and asthma in children at age three years. J Allergy Clin Immunol 127:262-264.
36. Håberg S, London S, Stigum H, Nafstad P, Nystad W. 2009. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Childhood 94:180-184.
37. Heederik, D, von Mutius, E. 2012. Does diversity of environmental microbial exposure matter for the occurrence of allergy and asthma? J Alergy Clin Immunol 130:44-50.
38. Hinz D, Bauer M, Roder S, Olek S, Huehn J, Sack U, Borte M, Simon JC, Lehmann I, Herberth G, et al. 2012. Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year. Allergy 67:380-389.
39. Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li Z, Tomfohr J, Bailey N, Potts EN, Whitehead G, Brass DM, et al. 2008. In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Investig 118:3462-3469.
40. Hylkema MN, Blacquiere MJ. 2009. Intrauterine effects of maternal smoking on sensitization, asthma, and chronic obstructive pulmonary disease. Proc Am Thorac Soc 6:660-662.
41. Isidoro-García M, Sanz C, García-Solaesa V, Pascual M, Pescador D, Lorente F, Davila I. 2011. PTGDR gene in asthma: a functional, genetic, and epigenetic study. Allergy 66:1553-1562.
42. Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, Adcock IM. 2002. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med 166:392-396.
43. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. 2001. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J 15:1110-1112.
44. Jacoby M, Gohrbandt S, Clausse V, Brons N, Muller C. 2012. Interindividual variability and co-regulation of DNA methylation differ among blood cell populations. Epigenetics 7:1421-1434.
45. Janson PC, Winerdal ME, Winqvist O. 2009. At the crossroads of T helper lineage commitment-epigenetics points the way. Biochim Biophys Acta 1790:906-919.
46. Jones B, Chen J. 2006. Inhibition of IFN-gamma transcription by site-specific methylation during T helper cell development. EMBO J 25:2443-2452.
47. Joubert BR, Håberg SE, Nilsen RM, Wang X, Vollset SE, Murphy SK, Huang Z, Hoyo C, Midttun O, Cupul-Uicab LA, et al. 2012. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect 120:1425-1431.
48. Jung KH, Hsu SI, Yan B, Moors K, Chillrud SN, Ross J, Wang S, Perzanowski MS, Kinney PL, Whyatt RM, et al. 2012. Childhood exposure to fine particulate matter and black carbon and the development of new wheeze between ages 5 and 7 in an urban prospective cohort. Environ Int 45:44-50.
49. Kalliola S, Pelkonen AS, Malmberg LP, Sarna S, Hamalainen M, Mononen I, Makela MJ. 2013. Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze. J Allergy Clin Immunol 131:730-735.
50. Koenen HJ, Smeets RL, Vink PM, van Rijssen E, Boots AM, Joosten I. 2008. Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 112:2340-2352.
51. Koppelman GH, Nawijn MC. 2011. Recent advances in the epigenetics and genomics of asthma. Curr Opin Allergy Clin Immunol 11:414-419.
52. Kuipers H, Lambrecht BN. 2004. The interplay of dendritic cells, Th2 cells and regulatory T cells in asthma. Curr Opin Immunol 16:702-708.
53. Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B. 2011. Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol 128:1077-1085.
54. Kuperman DA, Huang X, Koth LL, Chang GH, Dolganov GM, Zhu Z, Elias JA, Sheppard D, Erle DJ. 2002. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med 8:885-889.
55. Kuriakose J, Rosa MJ, Perzanowski M, Miller R. 2012. Bronchial nitric oxide flux may be better associated with inducible nitric oxide synthase promoter methylation. Am J Respir Crit Care Med 185:460-461.
56. Kwon NH, Kim JS, Lee JY, Oh MJ, Choi DC. 2008. DNA methylation and the expression of IL-4 and IFN-gamma promoter genes in patients with bronchial asthma. J Clin Immunol 28:139-146.
57. Lampi J, Canoy D, Jarvis D, Hartikainen AL, Keski Nisula L, Järvelin MR, Pekkanen J. 2011. Farming environment and prevalence of atopy at age 31: prospective birth cohort study in Finland. Clin Exp Allergy 41:987-993.
58. Larche M. 2007. Regulatory T cells in allergy and asthma. Chest 132:1007-1014.
59. Lee DU, Agarwal S, Rao A. 2002. Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16:649-660.
60. Lee KK, Workman JL. 2007. Histone acetyltransferase complexes: one size doesn't fit all. Nat Rev Mol Cell Biol 8:284-295.
61. Leynaert B, Neukirch C, Jarvis D, Chinn S, Burney P, Neukirch F. 2001. Does living on a farm during childhood protect against asthma, allergic rhinitis, and atopy in adulthood? Am J Respir Crit Care Med 164:1829-1834.
62. Li B, Carey M, Workman JL. 2007. The role of chromatin during transcription. Cell 128:707-719.
63. Litonjua AA, Carey VJ, Burge HA, Weiss ST, Gold DR. 1998. Parental history and the risk for childhood asthma. Does mother confer more risk than father? Am J Respir Crit Care Med 158:176-181.
64. Liu J, Ballaney M, Al-alem U, Quan C, Jin X, Perera F, Chen LC, Miller RL, et al. 2008. Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo. Toxicol Sci 102:76-81.
65. Liu J, Zhang L, Winterroth L, Garcia M, Weiman S, Wong J, Sunwoo JB, Nadeau KC. 2013. Epigenetically mediated pathogenic effects of phenanthrene on regulatory T cells. J Toxicol 2013:967029.
66. Lodrup Carlsen KC, Roll S, Carlsen KH, Mowinckel P, Wijga AH, Brunekreef B, Torrent M, Roberts G, Arshad SH, Kull I, et al. 2012. Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts. PLoS One 7:e43214.
67. Magdelijns F, Mommers M, Penders J, Smits L, Thijs C. 2011. Folic acid use in pregnancy and the development of atopy, asthma, and lung function in childhood. Pediatrics 128:e135-e144.
68. Masoli M, Fabian D, Holt S, Beasley R. 2004. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59:469-478.
69. Matsui EC, Matsui W. 2009. Higher serum folate levels are associated with a lower risk of atopy and wheeze. J Allergy Clin Immunol 123:1253-1259.
70. McConnell R, Berhane K, Yao L, Jerrett M, Lurmann F, Gilliland F, Kunzli N, Gauderman J, Avol E, Thomas D, et al. 2006. Traffic, susceptibility, and childhood asthma. Environ Health Perspect 114:766-772.
71. Miao CG, Yang YY, He X, Xu T, Huang C, Huang Y, Zhang L, Lv XW, Jin Y, Li J. 2013. New advances of microRNAs in the pathogenesis of rheumatoid arthritis, with a focus on the crosstalk between DNA methylation and the microRNA machinery. Cell Signal 25:1118-1125.
72. Michel S, Busato F, Genuneit J, Pekkanen J, Dalphin J-C, Riedler J, Mazaleyrat N, Weber J, Karvonen AM, Hirovnen MR, et al. 2013. Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy. Allergy 68:355-364.
73. Moffatt MF, Cookson WO. 1998. The genetics of asthma. Maternal effects in atopic disease. Clin Exp Allergy 28 (Suppl 1):56-61.
74. Morales E, Bustamante M, Vilahur N, Escaramis G, Montfort M, de Cid R, Garcia-Esteban R, Torrent M, Estivill X, Grimalt JO, et al. 2012. DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood. Am J Respir Cell Mol Biol 185:937-943.
75. Mukasa R, Balasubramani A, Lee YK, Whitley SK, Weaver BT, Shibata Y, Crawford GE, Hatton RD, Weaver CT. 2010. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage. Immunity 32:616-627.
76. Nadeau KC, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes JR, et al. 2010. Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol 126:845-852.
77. Noakes PS, Holt PG, Prescott SL. 2003. Maternal smoking in pregnancy alters neonatal cytokine responses. Allergy 58:1053-1058.
78. Ownby DR, Johnson CC, Peterson EL. 2002. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 288:963-972.
79. Patel MM, Hoepner L, Garfinkel R, Chillrud SN, Reyes A, Quinn JW, Perera F, Miller RL. 2009. Ambient metals, elemental carbon, and wheeze and cough in New York City children through 24 months of age. Am J Respir Crit Care Med 180:1107-1113.
80. Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller RL, Ho SM. 2009. Relation of DNA methylation of 5′-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 4:e4488.
81. Perzanowski MS, Chew GL, Divjan A, Jung KH, Ridder R, Tang D, Diaz D, Goldstein IF, Kinney PL, Rundle AG, et al. 2013. Early-life cockroach allergen and polycyclic aromatic hydrocarbon exposures predict cockroach sensitization among inner-city children. J Allergy Clin Immunol 131:886-893.
82. Polikepahad S, Knight JM, Naghavi AO, Oplt T, Creighton CJ, Shaw C, Diaz D, Goldstein IF, Kinney PL, Rundle AG, et al. 2010. Proinflammatory role for let-7 microRNAS in experimental asthma. J Biol Chem 285:30139-30149.
83. Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG. 1999. Development of allergen-specific T-cell memory in atopic and normal children. Lancet 353:196-200.
84. Rastogi D, Suzuki M, Greally JM. 2013. Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma. Sci Rep 3:2164.
85. Reik W. 2007. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447:425-432.
86. Remes ST, Iivanainen K, Koskela H, Pekkanen J. 2003. Which factors explain the lower prevalence of atopy amongst farmers' children? Clin Exp Allergy 33:427-434.
87. Riedler J, Braun-Fahrlander C, Eder W, Schreuer M, Waser M, Maisch S, Carr D, Schierl R, Nowak D, von Mutius E, et al. 2001. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129-1133.
88. Royce SG, Dang W, Ververis K, De Sampayo N, El-Osta A, Tang ML, Karagiannis TC. 2011. Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease. Epigenetics 6:1463-1470.
89. Runyon RS, Cachola LM, Rajeshuni N, Hunter T, Garcia M, Ahn R, Lurmann F, Krasnow R, Jack LM, Miller RL, et al. 2012. Asthma discordance in twins is linked to epigenetic modifications of T cells. PloS One 7:e48796.
90. Schaub B, Höppler S, Schleich I, Huehn J, Olek S, Wieczorek G, Illi S, von Mutius E. 2009. Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol 123:774-782.
91. Sears MR, Holdaway MD, Flannery EM, Herbison GP, Silva PA. 1996. Parental and neonatal risk factors for atopy, airway hyper-responsiveness, and asthma. Arch Dis Child 75:392-398.
92. Shang Y, Das S, Rabold R, Sham J, Mitzner W, Tang W. 2013. Epigenetic alterations by DNA methylation in house dust mite-induced airway hyperresponsiveness. Am J Respir Cell Mol Biol 49:279-287.
93. Singh S, Gundavarapu S, Peña-Philippides J, Rir-Sima-ah J, Mishra N, Wilder J, Langley RJ, Smith KR, Sopori ML. 2011. Prenatal secondhand cigarette smoke promotes Th2 polarization and impairs goblet cell differentiation and airway mucus formation. J Immunol 187:4542-4552.
94. Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR, Hou L, Nguyen C, Solon M, Nguyen C, Barczak AJ, et al. 2012. Airway epithelial miRNA expression is altered in asthma. Am J Respir Cell Mol Biol 186:965-974.
95. Soto-Ramírez N, Arshad SH, Holloway JW, Zhang H, Schauberger E, Ewart S, Patil V, Karmaus W. 2013. The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years. Clin Epigenet 5:1-8.
96. Spira-Cohen A, Chen LC, Kendall M, Lall R, Thurston GD. 2011. Personal exposures to traffic-related air pollution and acute respiratory health among Bronx schoolchildren with asthma. Environ Health Perspect 119:559-565.
97. Stefanowicz D, Hackett TL, Garmaroudi FS, Günther OP, Neumann S, Sutanto EN, Ling KM, Kobor MS, Kicic A, Stick SM, et al. 2012. DNA methylation profiles of airway epithelial cells and PBMCs from healthy, atopic and asthmatic children. PloS One 7:e44213.
98. Strachan DP, Wong HJ, Spector TD. 2001. Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins. J Allergy Clin Immunol 108:901-907.
99. Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G, Hodgdon K, Morgan W, Sorkness CA, Lemanske RF. Jr, et al. 2003. Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol 112:883-892.
100. Takemoto N, Kamogawa Y, Lee HJ, Kurata H, Arai K, O'Garra A. 2000. Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for Th2-specific cytokine gene cluster. J Immunol 165:6687-6691.
101. Talens RP, Boomsma DI, Tobi EW, Kremer D, Jukema JW, Willemsen G, Putter H, Slagboom PE, Heijmans BT. 2010. Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J 24:3135-3144.
102. Tang WY, Levin L, Talaska G, Cheung YY, Herbstman J, Tang D, Miller RL, Perera F, Ho SM. 2012. Maternal exposure to polycyclic aromatic hydrocarbons and 5′-CpG methylation of interferon-γ in cord white blood cells. Environ Health Perspect 120:1195-2000.
103. Tantisira KG, Colvin R, Tonascia J, Strunk RC, Weiss ST, Fuhlbrigge AL. 2008. Airway responsiveness in mild to moderate childhood asthma: sex influences on the natural history. Am J Respir Crit Care Med 178:325-331.
104. Tarantini L, Bonzini M, Apostoli P, Pegoraro V, Bollati V, Marinelli B, Cantone L, Rizzo G, Hou L, Schwartz J, et al. 2009. Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect 117:217-222.
105. Terry MB, Ferris JS, Pilsner R, Flom JD, Tehranifar P, Santella RM, Gamble MV, Susser E. 2008. Genomic DNA methylation among women in a multiethnic New York City birth cohort. Cancer Epidemiol Biomark Prevent 17:2306-2310.
106. Thomsen SF, Van Der Sluis S, Kyvik KO, Skytthe A, Backer V. 2010. Estimates of asthma heritability in a large twin sample. Clin Exp Allergy 40:1054-1061.
107. Thomson N. 2007. The role of environmental tobacco smoke in the origins and progression of asthma. Curr Allergy Asthma Rep 7:303-309.
108. Tsitsiou E, Williams AE, Moschos SA, Patel K, Rossios C, Jiang X, Adams OD, Macedo P, Booton R, Gibeon D, et al. 2012. Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma. J Allergy Clin Immunol 129:95-103.
109. Vaissière T, Sawan C, Herceg Z. 2008. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res 659:40-48.
110. Venkayya R, Lam M, Willkom M, Grunig G, Corry DB, Erle EJ. 2002. The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. Am J Respir Crit Care Med 26:202-208.
111. Von Mutius E. 2007. Asthma and allergies in rural areas of Europe. Proc Am Thorac Soc 4:212-216.
112. Vuillermin PJ, Ponsonby AL, Saffery R, Tang ML, Ellis JA, Sly P, Holt P. 2009. Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic disease. Allergy 64:348-353.
113. Webster RB, Rodriguez Y, Klimecki WT, Vercelli D. 2007. The human IL-13 locus in neonatal CD4+ T cells is refractory to the acquisition of a repressive chromatin architecture. J Allergy Clin Immunol 282:700-709.
114. Whitrow MJ, Moore VM, Rumbold AR, Davies MJ. 2009. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol 170:1486-1493.
115. Wong, C, Caspi A, Williams B, Craig IW, Houts R, Ambler A, Moffitt TE, Mill J. 2010. A longitudinal study of epigenetic variation in twins. Epigenetics 5:516-526.
116. Wu CJ, Yang CY, Chen YH, Chen CM, Chen LC, Kuo ML. 2012. The DNA methylation inhibitor 5-azacytidine increases regulatory T cells and alleviates airway inflammation in ovalbumin-sensitized mice. Int Arch Allergy Immunol 160:356-364.
117. Yang IV, Schwartz DA. 2012. Epigenetic mechanisms and the development of asthma. J Allergy Clin Immunol 130:1243-1255.
118. Yoshikawa T, Takata A, Otsuka M, Kishikawa T, Kojima K, Yoshida H, Koike K. 2012. Silencing of microRNA-122 enhances interferon-a signaling in the liver through regulating SOCS3 promoter methylation. Sci Rep 2:1-10.
119. Zeilinger S, Kühnel B, Klopp N, Baurecht H, Kleinschmidt A, Gieger C, Weidinger S, Lattka E, Adamski J, Peters A, et al. 2013. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PloS One 8:e63812.