The role of polymorphisms in ADAM33, a disintegrin and metalloprotease 33, in childhood asthma and lung function in two German populations.
BACKGROUND
ADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness. However, replication results have been inconclusive in smaller previous study populations probably due to inconsistencies in asthma phenotypes or yet unknown environmental influences. Thus, we tried to further elucidate the role of ADAM33 polymorphisms (SNPs) in a genetic analysis of German case control and longitudinal populations.


METHODS
Using MALDI-TOF, ten ADAM33 SNPs were genotyped in 1,872 children from the International Study of Asthma and Allergy in Childhood (ISAAC II) in a case control setting and further 824 children from the longitudinal cohort Multicentre Study of Allergy (MAS). In both populations the effects of single SNPs and haplotypes were studied and a gene environment analysis with passive smoke exposure was performed using SAS/Genetics.


RESULTS
No single SNP showed a significant association with doctor's diagnosis of asthma. A trend for somewhat more profound effects of ADAM33 SNPs was observed in individuals with asthma and BHR. Haplotype analyses suggested a minor effect of the ADAM33 haplotype H4 on asthma (p = 0.033) but not on BHR. Associations with non atopic asthma and baseline lung function were identified but no interaction with passive smoke exposure could be detected.


CONCLUSIONS
The originally reported association between ADAM33 polymorphisms and asthma and BHR could not be confirmed. However, our data may suggest a complex role of ADAM33 polymorphisms in asthma ethiology, especially in non atopic asthma.
Schedel
Michaela
M
University Children's Hospital, Ludwig Maximilian's University Munich, Germany. michael.kabesch@med.uni-muenchen.de
Depner
Martin
M
Schoen
Carola
C
Weiland
Stephan K
SK
Vogelberg
Christian
C
Niggemann
Bodo
B
Lau
Susanne
S
Illig
Thomas
T
Klopp
Norman
N
Wahn
Ulrich
U
von Mutius
Erika
E
Nickel
Renate
R
Kabesch
Michael
M
D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D005858:Germany; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D020641:Polymorphism, Single Nucleotide; D012129:Respiratory Function Tests
D051722:ADAM Proteins; C450441:ADAM33 protein, human