TY - JOUR T1 - Genetic variants in <em>Protocadherin-1</em>, bronchial hyperresponsiveness and asthma subphenotypes in German children JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - 1867 AU - Antoaneta Toncheva AU - Kathrin Suttner AU - Sven Michel AU - Norman Klopp AU - Thomas Illig AU - Christian Vogelberg AU - Andrea von Berg AU - Albrecht Bufe AU - Andrea Heinzmann AU - Otto Laub AU - Ernst Rietschel AU - Burkhard Simma AU - Thomas Frischer AU - Jon Genuneit AU - Erika von Mutius AU - Michael Kabesch Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/1867.abstract N2 - Background: Recently, Protocadherin-1 (PCDH1), located on chromosome 5q31-33, in the vicinity of the cytokine gene cluster containing several known candidate genes for asthma and allergy (interleukin-4, interleukin-5, interleukin-13 and RAD50), was reported as a novel susceptibility gene for bronchial hyperresponsiveness (BHR) and asthma.Objectives: We aimed to define linkage disequilibrium (LD) between the region comprising PCDH1 and the cytokine gene cluster. Next, for a comprehensive analysis of the PCDH1 locus we conducted detailed fine mapping of the PCDH1 region and investigated effects of single nucleotide polymorphisms (SNPs) in BHR, asthma and related phenotypes.Methods: Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping and imputation. Associations were investigated in a population of at least 1,303 (651 asthmatics) from two German study populations (MAGICS and ISAAC II).Results: No relevant LD between 14 PCDH1 tagging SNPs and 98 SNPs within the cytokine cluster was detected. There were no significant associations with BHR, atopy, allergic rhinitis and atopic eczema. However, rs7719391 was associated with asthma (OR=0.85, p=0.039) and non-atopic asthma (OR=0.69, p=0.009). The exonic SNP rs3797054 previously reported to be associated with BHR and asthma, was significantly associated with non-atopic asthma (OR=0.70, p=0.019) in our study. Significant associations with non-atopic asthma were observed also for rs11167761 (OR=1.54, p=0.021), rs3935792 (OR=1.32, p=0.039), rs2974704 (OR=0.43, p=0.009).Conclusions: PCDH1 polymorphisms may specifically affect the development of non-atopic asthma in children.These authors contributed equally: Mrs. Antoaneta Toncheva, Dr. Kathrin Suttner, and Mr. Sven Michel. ER -