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




The role of polymorphisms in ADAM33, a disintegrin and metalloprotease 33, in childhood asthma and lung function in two German populations - Download this document for free, or read online. Document in PDF available to download.

Respiratory Research

, 7:91

First Online: 19 June 2006Received: 28 March 2006Accepted: 19 June 2006

Abstract

BackgroundADAM33, 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.

MethodsUsing 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.

ResultsNo 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.

ConclusionThe 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.

AbbreviationsADAM33a disintegrin and metalloprotease 33

BHRbronchial hyperresponsiveness

EMexpectation-maximisation

FEV1forced expiratory volume in one second

FVCforced vital capacity

IgEimmunoglobulin E

ISAAC IIInternational Study of Asthma and Allergy in Childhood

LDlinkage disequilibrium

MASMulticentre Allergy Study

MALDI-TOFMatrix-assisted laser desorption time of flight

MEFmaximum expiratory flow

ORodds ratio

PC20Provocative concentration inducing a 20% fall in FEV1

PCRpolymerase chain reaction

SNPsingle nucleotide polymorphism

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Author: Michaela Schedel - Martin Depner - Carola Schoen - Stephan K Weiland - Christian Vogelberg - Bodo Niggemann - Susanne Lau

Source: https://link.springer.com/







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