Epigenetic changes in B lymphocytes associated with house dust mite allergic asthma

Although there is no doubt about the influence of the genetic background in the onset of the allergic diseases, Epigenome-Wide Association Studies are needed to elucidate the possible relationship between allergic diseases and epigenomic dysregulation. In this study we aimed to analyze the epigenetic patterns, in terms of DNA methylation, of three well-characterized populations of house dust mite allergic subjects, aspirin-intolerant asthmatics and controls. As a first, genome-wide phase, we used the HELP assay to study the methylation patterns in CD19+ B lymphocytes in these populations, and found that there are reproducible epigenetic differences at limited numbers of loci distinguishing the groups, corroborated by bisulphite MassArray in a second validation phase of an expanded 40 subject group. These validated epigenetic changes occur at loci characterized as important for the immune response. One such locus is a new candidate gene, CYP26A1, which shows differential methylation patterns and expression levels between groups. Our results suggest that epigenomic dysregulation may contribute to the susceptibility to allergic diseases, showing for the first time differences in DNA methylation between allergic and non-allergic healthy subjects, both globally and at specific loci. These observations indicate that the epigenome may offer new pathophysiological insights and therapeutic targets in atopic diseases.

[1]  A. Ross,et al.  Multiple cytochrome P-450 genes are concomitantly regulated by vitamin A under steady-state conditions and by retinoic acid during hepatic first-pass metabolism. , 2011, Physiological genomics.

[2]  Yifan Ma,et al.  Vitamin A and retinoic acid in the regulation of B-cell development and antibody production. , 2011, Vitamins and hormones.

[3]  M. Pascual,et al.  Epigenetic aspects of the allergic diseases. , 2010, Frontiers in bioscience.

[4]  D. Martino,et al.  Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease , 2010, Allergy.

[5]  Peter A. Jones,et al.  Epigenetics in cancer. , 2010, Carcinogenesis.

[6]  Lee E. Edsall,et al.  Human DNA methylomes at base resolution show widespread epigenomic differences , 2009, Nature.

[7]  Manel Esteller,et al.  Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies , 2009, The Lancet Neurology.

[8]  K. Berggård,et al.  Impact on allergic immune response after treatment with vitamin A , 2009, Nutrition & metabolism.

[9]  V. Clifton,et al.  Asthma and pregnancy: emerging evidence of epigenetic interactions in utero , 2009, Current opinion in allergy and clinical immunology.

[10]  Abdulrahman M. Al Senaidy Serum vitamin A and β-carotene levels in children with asthma. , 2009 .

[11]  Reid F. Thompson,et al.  High-resolution genome-wide cytosine methylation profiling with simultaneous copy number analysis and optimization for limited cell numbers , 2009, Nucleic acids research.

[12]  L. Joss-Moore,et al.  The developmental origins of adult disease , 2009, Current opinion in pediatrics.

[13]  Deliang Tang,et al.  Relation of DNA Methylation of 5′-CpG Island of ACSL3 to Transplacental Exposure to Airborne Polycyclic Aromatic Hydrocarbons and Childhood Asthma , 2009, PloS one.

[14]  J. Greally,et al.  The HELP assay. , 2009, Methods in molecular biology.

[15]  G. Gros,et al.  Epigenetic regulation of Th2 cytokine expression in atopic diseases. , 2008, Tissue antigens.

[16]  Quan Chen,et al.  An analytical pipeline for genomic representations used for cytosine methylation studies , 2008, Bioinform..

[17]  D. Vercelli,et al.  Discovering susceptibility genes for asthma and allergy , 2008, Nature Reviews Immunology.

[18]  C. Stephensen,et al.  Vitamin A Deficiency Decreases and High Dietary Vitamin A Increases Disease Severity in the Mouse Model of Asthma1 , 2008, The Journal of Immunology.

[19]  K. Boon,et al.  In utero supplementation with methyl donors enhances allergic airway disease in mice. , 2008, The Journal of clinical investigation.

[20]  M. Pascual,et al.  (CCTTT)n polymorphism of NOS2A in nasal polyposis and asthma: a case-control study. , 2008, Journal of investigational allergology & clinical immunology.

[21]  Adrian Bird,et al.  Perceptions of epigenetics , 2007, Nature.

[22]  D. J. Barker The origins of the developmental origins theory , 2007, Journal of internal medicine.

[23]  H. Mohrenweiser,et al.  The discovery of new coding alleles of human CYP26A1 that are potentially defective in the metabolism of all-trans retinoic acid and their assessment in a recombinant cDNA expression system , 2007, Pharmacogenetics and genomics.

[24]  M. Siimes,et al.  Retinol concentrations after birth are inversely associated with atopic manifestations in children and young adults , 2007, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[25]  G. Devereux The increase in the prevalence of asthma and allergy: food for thought , 2006, Nature Reviews Immunology.

[26]  Kenny Q. Ye,et al.  Comparative isoschizomer profiling of cytosine methylation: the HELP assay. , 2006, Genome research.

[27]  G. Joos,et al.  Cigarette smoke exposure facilitates allergic sensitization in mice , 2006, Respiratory research.

[28]  F. Gilliland,et al.  Maternal and grandmaternal smoking patterns are associated with early childhood asthma. , 2005, Chest.

[29]  L. Kalogjera,et al.  European Position Paper on Rhinosinusitis and Nasal Polyps , 2007 .

[30]  C. Davis,et al.  Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats. , 2003, The Journal of nutrition.

[31]  H. Kagechika,et al.  Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors. , 2003, International immunology.

[32]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[33]  G. Watt,et al.  Intergenerational 20 year trends in the prevalence of asthma and hay fever in adults: the Midspan family study surveys of parents and offspring , 2000, BMJ : British Medical Journal.

[34]  R. Russell The vitamin A spectrum: from deficiency to toxicity. , 2000, The American journal of clinical nutrition.

[35]  R. Kodell,et al.  Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  N. Åberg,et al.  Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991 , 1995, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[37]  M. de Carli,et al.  IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. , 1992, Journal of immunology.

[38]  D. P. Strachan,et al.  Hay fever, hygiene, and household size. , 1989, BMJ.