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Variable effects of environment due to genetics.

Variable effects of environment due to genetics. Turkish Thoracic Society 9 th Annual Congress Prof. Dr. Erika von Mutius University Children‘s Hospital Munich, Germany. Environmental factors for the development of childhood asthma. Protective factors : Day care Certain infections

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Variable effects of environment due to genetics.

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  1. Variable effects of environment due to genetics. Turkish Thoracic Society 9th Annual Congress Prof. Dr. Erika von Mutius University Children‘s Hospital Munich, Germany

  2. Environmental factors for the development of childhood asthma. Protective factors: Day care Certain infections Farming environment Risk factors: High body mass index Paracetamol use Traffic exposure Passive smoking

  3. Prevalence of asthma, hay fever and atopy among farmers' children in the ALEX Study % * * * * * * p< 0.05 Riedler et al. Lancet 2001

  4. Exposure to stables and/or farm milk in the 1. year of life. % ALEX-Study Riedler et al. Lancet 2001

  5. Mattress levels of endotoxin and muramic acid among farm and non-farm children.

  6. 100 1000 10000 100000 100 1000 10000 100000 100 1000 10000 100000 Hay fever Hay fever symptoms Atopy Braun-Fahrländer et al. NEJM 2002

  7. 100 1000 10000 100000 100 1000 10000 100000 Atopic wheeze Non-atopic wheeze Braun-Fahrländer et al. NEJM 2002

  8. Molecular Basis of LPS and Muramic Acid Interaction Bacteria MA LPS: Lipopolysaccharide LBP: LPS-binding protein MA: muramic acid LPS LPS LBP TLR2 CD14 LPS TLR4 NOD2 NF B

  9. High endotoxin exposure and TLR4/+45982 Lowendotoxin exposure and TLR4/+45982 % % 40 40 30 30 20 20 10 10 0 0 Current asthma symptoms Atopy Current hay fever symptoms Current asthma symptoms Asthma diagnosis Atopy Asthma diagnosis Current hay fever symptoms AA n=259 AG/GG n=45 AA n=266 AG/GG n=39 P=0.031 Eder et al, JACI 2004

  10. Farmers’ children and TLR2/-16933 BNonfarmers’ children (n=380) % % 40 40 p=0.023 30 30 p=0.012 20 p=0.004 p=0.01 20 10 10 0 0 Current asthma symptoms Atopy Current hay fever symptoms Current hay fever symptoms Current asthma symptoms Atopy Asthma diagnosis Asthma diagnosis TLR2/-16933 AT n=189 AA n=97 TT n=94 AA n=52 AT n=116 TT n=61 Eder et al, JACI 2004

  11. Environmental factors for the development of childhood asthma. Protective factors: Day care Certain infections Farming environment Risk factors: High body mass index Paracetamol use Traffic exposure Passive smoking

  12. Passive smoking and lung function decrements. A meta-analysis.

  13. Detoxification pathways David, AJRCCM2003

  14. GSTM1 deficiency, in utero ETS exposure and asthma in US children Gilliland, AJRCCM 2002

  15. GSTM1 Deficiency and ETS in the German ISAAC population Kabesch, Thorax 2004

  16. GSTT1 Deficiency and in utero ETS:impaired lung function development Kabesch, Thorax 2004

  17. Conclusions. • Environmental factors are important determinants for the development of childhood asthma. • The environmental exposure may decrease or increase the risk. • People are not uniformely sensitive to environmental influences depending on their genetic make up. • Gene*environment interactions highlight underlying pathomechanisms of disease inception.

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