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Allergic diseases and gene-environment interactions

Speaker: Erika von Mutius

29 September 2012


The 9th Symposium on Specific Allergy

Allergic diseases and gene-environment interactions

Erika von Mutius MD MSc Dr. von Hauner Children‘s Hospital, Ludwig Maximilian University Munich


Disclosures Erika von Mutius, University Children’s Hospital, Munich •

Lecture fees: ALK, Nestle,

Industry-sponsored grant (institution): Airsonnett

Consultancy: Protectimmun, Novartis


25

25

20

20 Phenotype

Phenotype

Genetic Effects:

15 10

15 10

5

5

0

0

A

B

Genotype

A

B

Genotype


GABRIEL Study: First GWAS

Nature 2007


GABRIEL Study: First GWAS ORMDL3

Moffat et al, Nature 2007


ORMDL3 Associates with Childhood Onset Asthma

Bouzigon E et al. N Engl J Med 2008;359:1985-1994


Adults

Children

Chromosome 17 ORMDL3 / GSDMB


Phenotype

Environmental Effects: 25

Environmental exposure:

20

dotted green line = unexposed; solid red line = exposed.

15 10 5 0 A

B

Genotype

The environment has an effect, but the genotype does not have an effect.


Fall of the Berlin wall 1989.


Prevalence of asthma, airway hyperresponsiveness and atopy in

East and West Germany 1989/92.

%

40

East Germany West Germany

35 30 25 20 15 10 5 0 Asthma ever

Current asthma

AHR

Hay fever

Atopy

Von Mutius et al, AJRCCM 1994


Decreased Hospital Admission for Asthma After Tobacco Smoke Ban in Scotland

15 % Abnahme der Asthmaaufnahmerate

Mackay et al, NEJM 2010


Gene*Environment Interactions: 25

Environmental exposure: Phenotype

20

dotted green line= exposed; solid red line=unexposed.

15 10 5

The environment has an effect

0 A

B

Genotype

in subjects with a certain genotype, but not in others.


Detoxification of Environmental Tobacco Smoke and Pollutants.

David, AJRCCM2003


Effect of in utero ETS Exposure on Asthma According to GSTM1 Deficiency.

Gilliland, AJRCCM 2002


GSTT1 Deficiency and in utero ETS: Impaired Lung Function Development. 110

% predicted

100

90

80

70

60 FVC

FEV1

PEF

MEF 25

no ETS in Utero & GST T1+ no ETS in Utero & GST T1ETS in Utero & GST T1+ ETS in Utero & GST T1-

MEF 50

MEF 75

Kabesch et al, Thorax 2004


Other Gene*Environment Interactions with Passive Smoke Exposure. 

CD14 (Choudhry et al, AJRCCM 2005)

IL10 (Karjalainen et al, Clin Exp Allergy 2003)

IL13 (Sadeghnejad et al, Resp Res 2008)

ILR1N (Ramadas et al, Eur Resp J 2007)

ORMDL3 (Bouzigon et al, NEJM 2008) No individual risk prediction possible.


Gene*Environment Interactions in Asthma. ďƒ˜

Asthma is a complex disease driven by hereditary components and environmental influences.

ďƒ˜

Many gene*environment interactions are likely to play a role for the manifestation of the various asthma phenotypes.

Erika von Mutius  
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