variable effects of environment due to genetics
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/1.jpg)
Variable effects of environment due to genetics.
Turkish Thoracic Society 9th Annual Congress
Prof. Dr. Erika von Mutius
University Children‘s Hospital
Munich, Germany
![Page 2: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/2.jpg)
Environmental factors for the development of childhood asthma.
Protective factors:Day careCertain infectionsFarming environment
Risk factors:High body mass indexParacetamol useTraffic exposurePassive smoking
![Page 3: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/3.jpg)
![Page 4: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/4.jpg)
![Page 5: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/5.jpg)
Prevalence of asthma, hay fever and Prevalence of asthma, hay fever and atopy among farmers' children in the atopy among farmers' children in the ALEX StudyALEX Study
%
0
5
10
15
20
25
30
35
40
Asthmadiagnosis
Asthmasymptoms
Hay feverdiagnosis
Hay feversymptoms
Atopy
Non-Farmers (n=493)Farmers (n=319)
* * * *
*
* p< 0.05
Riedler et al. Lancet 2001
![Page 6: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/6.jpg)
![Page 7: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/7.jpg)
Exposure to stables and/or farm
milk in the 1. year of life.
11.8
1.4
14.8
2.8
16
3.2
19.8
5.1
32.9
12.4
0
5
10
15
20
25
30
35
Asthma diagnosisAsthma symptoms Hay feverdiagnosis
Hay feversymptoms
Atopy
No exposureMilk onlyStable onlyStable and milk
%
ALEX-StudyRiedler et al. Lancet 2001
![Page 8: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/8.jpg)
Mattress levels of endotoxin and muramic
acid among farm and non-farm children.
0
20
40
60
80
100
120
140
160
180
Muramic acid µg /m2
0
5000
10000
15000
20000
25000
30000
Endotoxin EU/m2
FarmchildrenNon farmchildren
![Page 9: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/9.jpg)
2 3 4 5
Endotoxin Load in Mattress [EU/m2] (log scale)
510
15A
dj. P
reva
lenc
e of
Hay
Fev
er (%
)
100 1000 10000 1000002 3 4 5
Endotoxin Load in Mattress [EU/m2] (log scale)
010
2030
Adj
.ust
ed P
reva
lenc
e of
Hay
Fev
er S
ympt
oms
(%)
100 1000 10000 1000002 3 4 5
Endotoxin Load in Mattress [EU/m2] (log scale)
1015
20A
dj. P
reva
lenc
e of
Ato
pic
Sen
sitiz
atio
n (%
)
100 1000 10000 100000
Hay fever Hay fever symptoms Atopy
Braun-Fahrländer et al. NEJM 2002
![Page 10: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/10.jpg)
2 3 4 5
Endotoxin Load in Mattress [EU/m2] (log scale)
24
68
Ad
j. P
reva
len
ce o
f N
on
-Ato
pic
Wh
ee
ze (
%)
100 1000 10000 1000002 3 4 5
Endotoxin Load in Mattress [EU/m2] (log scale)
24
68
1012
Adj
. Pre
vale
nce
of A
topi
c W
heez
e (%
)
100 1000 10000 100000
Atopic wheeze Non-atopic wheeze
Braun-Fahrländer et al. NEJM 2002
![Page 11: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/11.jpg)
LPS: Lipopolysaccharide
LBP: LPS-binding protein
MA: muramic acid
Molecular Basis of LPS and Muramic Acid Interaction
Bacteria
LPS
LPS
TLR4
TLR2CD14
LBP
NF B
MA
LPS
NOD2
![Page 12: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/12.jpg)
0
10
20
30
40
High endotoxin exposure and TLR4/+45982
Asthma diagnosis
Currentasthma
symptoms
Atopy Currenthay fever
symptoms
AA n=259 AG/GG n=45
%
0
10
20
30
40
Low endotoxin exposure and TLR4/+45982
Asthma diagnosis
Atopy Currenthay fever
symptoms
AA n=266 AG/GG n=39
%
Currentasthma
symptoms
P=0.031
Eder et al,JACI 2004
![Page 13: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/13.jpg)
Farmers’ children and TLR2/-16933
0
10
20
30
40
Asthma diagnosis
Currentasthma
symptoms
Atopy Currenthay fever
symptoms
AA n=52 AT n=116 TT n=61
%
p=0.012 p=0.004
p=0.023
p=0.01
B Nonfarmers’ children (n=380)
0
10
20
30
40
Asthma diagnosis
Currentasthma
symptoms
Atopy Current hay fever
symptoms
%
TLR2/-16933 AA n=97 TT n=94AT n=189
Eder et al,
JACI 2004
![Page 14: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/14.jpg)
Environmental factors for the development of childhood asthma.
Protective factors:Day careCertain infectionsFarming environment
Risk factors:High body mass indexParacetamol useTraffic exposurePassive smoking
![Page 15: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/15.jpg)
![Page 16: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/16.jpg)
Passive smoking and
lung function
decrements.
A meta-analysis.
![Page 17: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/17.jpg)
Detoxification pathways
David, AJRCCM2003
![Page 18: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/18.jpg)
GSTM1 deficiency, in utero ETS exposure and asthma in US children
Gilliland, AJRCCM 2002
![Page 19: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/19.jpg)
GSTM1 Deficiency and ETS in the German ISAAC population
Kabesch, Thorax 2004
![Page 20: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/20.jpg)
FVC FEV1 PEF MEF 25 MEF 50 MEF 75
% p
red
icte
d
60
70
80
90
100
110
no ETS in Utero & GST T1+no ETS in Utero & GST T1-ETS in Utero & GST T1+ETS in Utero & GST T1-
GSTT1 Deficiency and in utero ETS:impaired lung function development
Kabesch, Thorax 2004
![Page 21: Variable effects of environment due to genetics](https://reader036.vdocuments.us/reader036/viewer/2022062304/568133e1550346895d9ad311/html5/thumbnails/21.jpg)
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.