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Toncheva, A.A.* ; Suttner, K.* ; Michel, S.* ; Klopp, N. ; Illig, T. ; Balschun, T.* ; Vogelberg, C.* ; von Berg, A.* ; Bufe, A.* ; Heinzmann, A.* ; Laub, O.* ; Rietschel, E.* ; Simma, B.* ; Frischer, T.* ; Genuneit, J.* ; von Mutius, E.* ; Kabesch, M.*

Genetic variants in Protocadherin-1, bronchial hyper-responsiveness, and asthma subphenotypes in German children.

Pediatr. Allergy Immunol. 23, 636-641 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Background: Recently, Protocadherin-1 (PCDH1) was reported as a novel susceptibility gene for bronchial hyper-responsiveness (BHR) and asthma. PCDH1 is located on chromosome 5q31-33, in the vicinity of several known candidate genes for asthma and allergy. To exclude that the associations observed for PCDH1 originate from the nearby cytokine cluster, an extensive linkage disequilibrium (LD) analysis was performed. Effects of polymorphisms in PCDH1 on asthma, BHR, and related phenotypes were studied comprehensively. Methods: Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping, and imputation. LD was assessed by Haploview 4.2 software. Associations were investigated in a population of 1454 individuals (763 asthmatics) from two German study populations [MAGICS and International Study of Asthma and Allergies in Childhood phase II (ISAAC II)] using logistic regression to model additive effects. Results: No relevant LD between PCDH1 tagging polymorphisms and 98 single nucleotide polymorphisms within the cytokine cluster was detected. While BHR was not associated with PCDH1 polymorphisms, significant associations with subphenotypes of asthma were observed. Conclusion: Protocadherin-1 polymorphisms may specifically affect the development of non-atopic asthma in children. Functional studies are needed to further investigate the role of PCDH1 in BHR and asthma development.
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Publication type Article: Journal article
Document type Scientific Article
Keywords 5q31 Cytokine Gene Cluster ; Linkage Disequilibrium ; Protocadherin-1 ; Polymorphism; Association ; Expression ; Risk
Language english
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 0905-6157
e-ISSN 1399-3038
Journal Pediatric Allergy and Immunology
Quellenangaben Volume: 23, Issue: 7, Pages: 636-641 Article Number: , Supplement: ,
Publisher Wiley
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504200-001
PubMed ID 23050600
DOI 10.1111/j.1399-3038.2012.01334.x
WOS ID WOS:000310552000006
Scopus ID 84868192328
Erfassungsdatum 2012-11-29
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