British Society for Allergy and Clinical Immunology Abstracts of the 2012 Annual Meeting

S – BASIC SCIENCE IL13 SNP (rs1800925) genotype and DNA methylation associated with lung function in adolescent females V.K. Patil*, J.W. Holloway, H. Zhang, S. Ewart, S.H. Arshad and W. Karmaus *David Hide Asthma and Allergy Research Centre, United Kingdom, University of Southampton, United Kingdom, University of South Carolina, USA, Michigan State University, USA Background Interleukin (IL) 13 polymorphisms together with environmental exposures such as tobacco smoke exposure have been associated with asthma and lung function. However, both genetic and environmental exposure studies fail to explain the variability in susceptibility and disease phenotypes. The epigenome, particularly DNA methylation, represents a site of molecular interaction between the environment and the genome and may play an important role in determining phenotype. Thus, we aimed to explore the effect of the IL13 polymorphism rs1800925, the level of methylation at CpG site cg13566430 in the promoter region of the IL13 gene, and their interaction on lung function (FEV1/FVC). Methods Subjects from the 1989 Isle of Wight birth cohort (n = 1456) were followed up at 1, 2, 4, 10 and 18 years. At 18 years 839/1313 had spirometry. Bloods were collected from 552/1313 out of which 245 were female. Illumina Human450K methylation arrays were used to assess DNA methylation levels at > 484 000 CpG sites in 245 female participants. Linear regression and linear mixed models were used to analyze the data. Results Genotype, methylation and spirometry were available for 226 females. Methylation at cg13566430 differed by genotype (P = 0.017). IL13 rs1800925 genotype was not significantly associated with FEV1/FVC independently. However its interaction with methylation at cg13566430 was significantly associated with FEV1/FVC (Table 1). Conclusion IL13 rs1800925 genotype-dependent DNA methylation was seen at cg13566430 and the interaction between genotype and DNA methylation was significantly associated with FEV1/FVC in adolescent females. DNA methylation is likely to modify the effect size of the impact of genetic variants that play a role in the development of asthma. Effect of IL13 rs1800925 genotypes and cg13566430 methylation (main effects) on FEV1/FVC. Main effects N = 226 FEV1/FVC (mean) P value AA 8 (3.5%) 0.905 0.083 AG 63 (27.8%) 0.873 0.528 GG 155 (58.2%) 0.877 Reference CpG 13566430 methylation 0.0432 Effect of interaction of genotype and metylation on FEV1/ FVC Interactions P value AA*methylation 0.033 AG*methylation 0.031 GG*methylation Reference doi: 10.1111/cea.12033 Clinical & Experimental Allergy, 42, 1815–1862 © 2012 Blackwell Publishing Ltd