These authors contributed equally to this article.
Genetic variants in Protocadherin-1, bronchial hyper-responsiveness, and asthma subphenotypes in German children
Article first published online: 11 OCT 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Pediatric Allergy and Immunology
Volume 23, Issue 7, pages 636–641, November 2012
How to Cite
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. and Kabesch, M. (2012), Genetic variants in Protocadherin-1, bronchial hyper-responsiveness, and asthma subphenotypes in German children. Pediatric Allergy and Immunology, 23: 636–641. doi: 10.1111/j.1399-3038.2012.01334.x
- Issue published online: 29 OCT 2012
- Article first published online: 11 OCT 2012
- Accepted for publication 16 May 2012
- 5q31 cytokine gene cluster;
- linkage disequilibrium;
- Protocadherin-1 ;
To cite this article: Toncheva AA, 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 2012.
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.