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


CONCLUSIONS
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.
Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
Antoaneta A
AA
Toncheva
Kathrin
K
Suttner
Sven
S
Michel
Norman
N
Klopp
Thomas
T
Illig
Tobias
T
Balschun
Christian
C
Vogelberg
Andrea
A
von Berg
Albrecht
A
Bufe
Andrea
A
Heinzmann
Otto
O
Laub
Ernst
E
Rietschel
Burkhard
B
Simma
Thomas
T
Frischer
Jon
J
Genuneit
Erika
E
von Mutius
Michael
M
Kabesch
D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D005858:Germany; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D000091363:Protocadherins
D015820:Cadherins; D016207:Cytokines; C081683:PCDH1 protein, human; D000091363:Protocadherins