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.
Conclusion: 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.