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2016 | Humangenetik | OriginalPaper | Buchkapitel

3. Genetik und Epigenetik von allergischen Erkrankungen und Asthma

verfasst von : S. Weidinger, Prof. Dr. med., M. Kabesch, Prof. Dr. med. univ., E. Rodriguez, Dr. rer. nat.

Erschienen in: Allergologie

Verlag: Springer Berlin Heidelberg

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Zusammenfassung

Allergische Erkrankungen sind sehr heterogene Krankheitsbilder, deren Entstehung und Verlauf in erheblichem Maße durch erbliche Faktoren beeinflusst werden. Durch den Einsatz moderner molekulargenetischer Methoden konnten innerhalb der letzten 10 Jahre eine Vielzahl bislang unbekannter genetischer Risikofaktoren identifiziert werden. Obwohl die zugrunde liegenden kausalen Mechanismen häufig noch unzureichend verstanden sind, haben die bisherigen Erkenntnisse schon jetzt pathophysiologische Konzepte nachhaltig verändert und wichtige Stimuli zur Entwicklung gezielter präventiver und therapeutischer Ansätze gegeben. Insbesondere wurde die wichtige Bedeutung epithelialer Mechanismen in der Ätiologie allergischer Erkrankungen deutlich. Erste Studien deuten außerdem darauf hin, dass epigenetischen Faktoren in der Pathogenese eine wichtige Rolle zukommt. Die fortschreitende Entwicklung molekularbiologischer Strategien und die Integration klinischer und molekularer Daten werden zur weiteren Aufklärung erblicher Mechanismen und zur Abgrenzung von Patientensubgruppen beitragen und so die Entwicklung einer stratifizierten Medizin im Bereich der Allergologie befördern.

Antequera F (2003) Structure, function and evolution of CpG island promoters. Cell Mol Life Sci 60: 1647–1658

Asai Y, Greenwood C, Hull PR et al. (2013) Filaggrin gene mutation associations with peanut allergy persist despite variations in peanut allergy diagnostic criteria or asthma status. J Allergy Clin Immunol 132: 239–242

Barnes KC (2010) An update on the genetics of atopic dermatitis: scratching the surface in 2009. J Allergy Clin Immunol 125: 16–29 e11–11; quiz 30–11

Barnes PJ (2009) Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 6: 693–696

Barnes PJ (2013) Theophylline. Am J Respir Crit Care Med 188: 901–906

Binia A, Kabesch M (2012) Respiratory medicine – genetic base for allergy and asthma. Swiss Med Wkly 142: w13612

Bird A (2002) DNA methylation patterns and epigenetic memory. Genes & Development 16: 6–21

Bonnelykke K, Matheson MC, Pers TH et al. (2013) Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet 45: 902–906

Breton CV, Byun HM, Wenten M et al. (2009) Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med 180: 462–467

Brown SJ, Asai Y, Cordell HJ et al. (2011) Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 127: 661–667

Cai SC, Chen H, Koh WP et al. (2012) Filaggrin mutations are associated with recurrent skin infection in Singaporean Chinese patients with atopic dermatitis. Br J Dermatol 166: 200–203

Cantero-Recasens G, Fandos C, Rubio-Moscardo F et al. (2010) The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet 19: 111–121

Carreras-Sureda A, Cantero-Recasens G, Rubio-Moscardo F et al. (2013) ORMDL3 modulates store-operated calcium entry and lymphocyte activation. Hum Mol Genet 22: 519–530

Chakravarti A, Clark AG, Mootha VK (2013) Distilling pathophysiology from complex disease genetics. Cell 155: 21–26

Chen H, Common JE, Haines RL et al. (2011) Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations. The British journal of dermatology 165: 106–114

Cooke R, Van Der Veer A (1916) Human sensitization. J Immunol: 201–305

Deckers IA, Mclean S, Linssen S et al. (2012) Investigating international time trends in the incidence and prevalence of atopic eczema 1990–2010: a systematic review of epidemiological studies. PLoS One 7: e39803

Ding L, Abebe T, Beyene J et al. (2013) Rank-based genome-wide analysis reveals the association of ryanodine receptor-2 gene variants with childhood asthma among human populations. Hum Genomics 7: 16

Ellinghaus D, Baurecht H, Esparza-Gordillo J et al. (2013) High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet 45: 808–812

Esparza-Gordillo J, Weidinger S, Folster-Holst R et al. (2009) A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 41: 596–601

Ezell SA, Polytarchou C, Hatziapostolou M et al. (2012) The protein kinase Akt1 regulates the interferon response through phosphorylation of the transcriptional repressor EMSY. Proc Natl Acad Sci U S A 109: E613–621

Ferreira MA, Matheson MC, Duffy DL et al. (2011a) Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 378: 1006–1014

Ferreira MA, Mcrae AF, Medland SE et al. (2011b) Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia. Eur J Hum Genet 19: 458–464

Flohr C, Johansson SG, Wahlgren CF et al. (2004) How atopic is atopic dermatitis? J Allergy Clin Immunol 114: 150–158

Flohr C, England K, Radulovic S et al. (2010) Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age. Br J Dermatol 163: 1333–1336

Forno E, Lasky-Su J, Himes B et al. (2012) Genome-wide association study of the age of onset of childhood asthma. J Allergy Clin Immunol 130: 83–90 e84

Gao PS, Rafaels NM, Hand T et al. (2009) Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. J Allergy Clin Immunol 124: 507–513, 513.e501–507

Granada M, Wilk JB, Tuzova M et al. (2012) A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. J Allergy Clin Immunol 129: 840–845 e821

Ha SG, Ge XN, Bahaie NS et al. (2013) ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48. Nat Commun 4: 2479

Hancock DB, Romieu I, Shi M et al. (2009) Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children. PLoS genetics 5: e1000623

Hardy J, Singleton A (2009) Genomewide association studies and human disease. N Engl J Med 360: 1759–1768

Himes BE, Hunninghake GM, Baurley JW et al. (2009) Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am J Hum Genet 84: 581–593

Hinds DA, Mcmahon G, Kiefer AK et al. (2013) A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Nat Genet 45: 907–911

Hirota T, Takahashi A, Kubo M et al. (2011) Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet 43: 893–896

Hirota T, Takahashi A, Kubo M et al. (2012) Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 44: 1222–1226

Hotze M, Baurecht H, Rodriguez E et al. (2014) Increased efficacy of omalizumab in atopic dermatitis patients with wild-type filaggrin status and higher serum levels of phosphatidylcholines. Allergy 69: 132–135

Howell MD, Kim BE, Gao P et al. (2007) Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 120: 150–155

Hsu TL, Chang YC, Chen SJ et al. (2002) Modulation of dendritic cell differentiation and maturation by decoy receptor 3. J Immunol 168: 4846–4853

Hudson TJ (2006) Skin barrier function and allergic risk. Nat Genet 38: 399–400

Irvine AD (2007) Fleshing out filaggrin phenotypes. J Invest Dermatol 127: 504–507

Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13: 484–492

Kabesch M, Adcock IM (2012) Epigenetics in asthma and COPD. Biochimie 94: 2231–2241

Kretschmer A, Moller G, Lee H et al. (2014) A common atopy-associated variant in the Th2 cytokine locus control region impacts transcriptional regulation and alters SMAD3 and SP1 binding. Allergy 69: 632–642

Lasky-Su J, Himes BE, Raby BA et al. (2012) HLA-DQ strikes again: genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults. Clin Exp Allergy 42: 1724–1733

Levin AM, Mathias RA, Huang L et al. (2013) A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations. J Allergy Clin Immunol 131: 1176–1184

Li X, Howard TD, Zheng SL et al. (2010) Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. J Allergy Clin Immunol 125: 328–335 e311

Lin WW, Hsieh SL (2011) Decoy receptor 3: a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer. Biochem Pharmacol 81: 838–847

Manolio TA (2010) Genomewide association studies and assessment of the risk of disease. N Engl J Med 363: 166–176

Manolio TA, Collins FS, Cox NJ et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747–753

Marchini J, Howie B (2010) Genotype imputation for genome-wide association studies. Nature reviews. Genetics 11: 499–511

Michel S, Busato F, Genuneit J 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

Moffatt MF, Kabesch M, Liang L et al. (2007) Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448: 470–473

Moffatt MF, Gut IG, Demenais F et al. (2010) A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363: 1211–1221

Nakanishi K, Yoshimoto T, Tsutsui H et al. (2001) Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev 12: 53–72

Noguchi E, Sakamoto H, Hirota T et al. (2011) Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations. PLoS genetics 7: e1002170

Novak N, Bieber T (2003) Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol 112: 252–262

Novak N, Baurecht H, Schafer T et al. (2007) Loss-of-Function Mutations in the Filaggrin Gene and Allergic Contact Sensitization to Nickel. J Invest Dermatol 128: 1430–1435

Palmer CN, Irvine AD, Terron-Kwiatkowski A et al. (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38: 441–446

Paternoster L, Standl M, Chen CM et al. (2012) Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet 44: 187–192

Pellerin L, Henry J, Hsu CY et al. (2013) Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin. J Allergy Clin Immunol 131: 1094–1102

Ramasamy A, Curjuric I, Coin LJ et al. (2011) A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J Allergy Clin Immunol 128: 996–1005

Ramasamy A, Kuokkanen M, Vedantam S et al. (2012) Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. PLoS One 7: e44008

Rodriguez E, Baurecht H, Herberich E et al. (2009) Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol 123: 1361–1370 e1367

Rodriguez E, Baurecht H, Wahn AF et al. (2014) An Integrated Epigenetic and Transcriptomic Analysis Reveals Distinct Tissue-Specific Patterns of DNA Methylation Associated with Atopic Dermatitis. J Invest Dermatol

Ross-Hansen K, Menne T, Johansen JD et al. (2011) Nickel reactivity and filaggrin null mutations--evaluation of the filaggrin bypass theory in a general population. Contact Dermatitis 64: 24–31

Savinko T, Karisola P, Lehtimaki S et al. (2013) ST2 regulates allergic airway inflammation and T-cell polarization in epicutaneously sensitized mice. The Journal of investigative dermatology 133: 2522–2529

Schmitz RJ, Schultz MD, Urich MA et al. (2013) Patterns of population epigenomic diversity. Nature 495: 193–198

Siracusa MC, Saenz SA, Hill DA et al. (2011) TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477: 229–233

Sleiman PM, Flory J, Imielinski M et al. (2010) Variants of DENND1B associated with asthma in children. N Engl J Med 362: 36–44

Smith FJ, Irvine AD, Terron-Kwiatkowski A et al. (2006) Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 38: 337–342

Stefanowicz D, Hackett TL, Garmaroudi FS et al. (2012) DNA methylation profiles of airway epithelial cells and PBMCs from healthy, atopic and asthmatic children. PLoS One 7: e44213

Stepensky P, Keller B, Buchta M et al. (2013) Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. J Allergy Clin Immunol 131: 477–485 e471

Sun LD, Xiao FL, Li Y et al. (2011) Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat Genet 43: 690–694

Tammen SA, Friso S, Choi SW (2013) Epigenetics: the link between nature and nurture. Mol Aspects Med 34: 753–764

Tang TS, Bieber T, Williams HC (2012) Does »autoreactivity« play a role in atopic dermatitis? J Allergy Clin Immunol 129: 1209–1215 e1202

Tantisira KG, Damask A, Szefler SJ et al. (2012) Genome-wide association identifies the T gene as a novel asthma pharmacogenetic locus. AmJ Respir Crit Care Med 185: 1286–1291

Torgerson DG, Ampleford EJ, Chiu GY et al. (2011) Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43: 887–892

Van Beijsterveldt CE, Boomsma DI (2007) Genetics of parentally reported asthma, eczema and rhinitis in 5-yr-old twins. Eur Respir J 29: 516–521

Vercelli D (2008) Discovering susceptibility genes for asthma and allergy. Nature Rev Immunol 8: 169–182

Visser MJ, Landeck L, Campbell LE et al. (2013) Impact of atopic dermatitis and loss-of-function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis. Br J Dermatol 168: 326–332

Wan YI, Shrine NR, Soler Artigas M et al. (2012) Genome-wide association study to identify genetic determinants of severe asthma. Thorax 67: 762–768

Weidinger S, Rodriguez E, Stahl C et al. (2007) Filaggrin mutations strongly predispose to early-onset and extrinsic atopic dermatitis. J Invest Dermatol 127: 724–726

Weidinger S, Baurecht H, Wagenpfeil S et al. (2008a) Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk. J Allergy Clin Immunol 122:560–568 e564

Weidinger S, Gieger C, Rodriguez E et al. (2008b) Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS genetics 4: e1000166

Weidinger S, O’Sullivan M, Illig T et al. (2008c) Filaggrin mutations, atopic eczema, hay fever, and asthma in children. J Allergy Clin Immunol

Weidinger S, Baurecht H, Naumann A et al. (2010) Genome-wide association studies on IgE regulation: are genetics of IgE also genetics of atopic disease? Current opinion in allergy and clinical immunology 10:408–417

Weidinger S, Willis-Owen SA, Kamatani Y et al. (2013) A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Hum Mol Genet 22: 4841–4856

Titel: Genetik und Epigenetik von allergischen Erkrankungen und Asthma
verfasst von: S. Weidinger, Prof. Dr. med.
M. Kabesch, Prof. Dr. med. univ.
E. Rodriguez, Dr. rer. nat.
Verlag: Springer Berlin Heidelberg
Buch: Allergologie
Print ISBN: 978-3-642-37202-5

Electronic ISBN: 978-3-642-37203-2

Copyright-Jahr: 2016
DOI: https://doi.org/10.1007/978-3-642-37203-2_3

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Die Highlights vom Kongress des American College of Cardiology 2024

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3. Genetik und Epigenetik von allergischen Erkrankungen und Asthma

Zusammenfassung

Passend zum Thema

Es wäre so einfach, ein Leben zu retten – Wenn man nur daran denkt…

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

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Passend zum Thema

Es wäre so einfach, ein Leben zu retten – Wenn man nur daran denkt…