Research

The role of polymorphisms in ADAM33, a disintegrin and metalloprotease 33, in childhood asthma and lung function in two German populations

Michaela Schedel^1* , Martin Depner^1* , Carola Schoen¹ , Stephan K Weiland² , Christian Vogelberg³ , Bodo Niggemann⁴ , Susanne Lau⁴ , Thomas Illig⁵ , Norman Klopp⁵ , Ulrich Wahn⁴ , Erika von Mutius¹ , Renate Nickel⁴ and Michael Kabesch¹

¹  University Children's Hospital, Ludwig Maximilian's University Munich, Germany

²  Department of Epidemiology, University of Ulm, Germany

³  University Children's Hospital Dresden, Germany

⁴  Department of Pediatric Pneumology and Immunology, Charité Humbolt University Berlin, Germany

⁵  Institute of Epidemiology, GSF -Research Centre for Environment and Health, Neuherberg, Germany

author email corresponding author email* Contributed equally

Respiratory Research 2006, 7:91doi:10.1186/1465-9921-7-91

Published:	19 June 2006

Abstract

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.