*Co-last authors

Interleukin 6 is an inflammatory cytokine involved in asthma, and few studies reported associations of IL6 variants with asthma/atopic asthma. However, no study has used an approach including genes involved in IL6-related biological pathways.

We aimed to 1) confirm associations between IL6 and asthma, and 2) identify new genetic variants associated to asthma located in genes involved in at least one inflammatory/immunity pathway including IL6.

Association analyses between Single Nucleotide Polymorphisms (SNPs) and asthma/atopic asthma were performed by logistic model among 1437 adults (43 years old, 49% men, 43% asthma, 29% atopic asthma) of the 1st follow-up of the Genetics and Environment of Asthma study (EGEA). Asthma was defined by standardized questions or by being recruited as asthmatic cases at inclusion, and atopic asthma by Skin Prick Test positivity. For top-SNPs (p<0.01) found in EGEA, replication analyses in the Finnish Environment and Asthma study (FEAS) and meta-analyses were performed.

Previous associations of SNPs in IL6 including those found in FEAS were replicated, especially with atopic asthma (p=0.02). Regarding SNPs located in genes from IL6-related pathways, a significant association was found by meta-analysis (p=4.5x10-6) between one SNP located in PTPRC and atopic asthma. The 2nd and 3rd top-SNPs were located in TNFRSF1B (p=10-5) and in PTPRE (p=2x10-5), results being almost significant.

The study 1) replicated associations between IL6 and atopic asthma, and 2) identified, based on a ?pathway approach?, PTPRC, a gene associated to asthma in previous GWAS, and new promising genes TNFRSF1B and PTPRE. Replication analyses in other independent samples are ongoing.