Abstract
Background We reported strong independent and joint effects of family asthma and second-hand smoke exposure (SHS) on the risk of adult-onset asthma (AJRCCM 2013). For interleukin 6 (IL6), an inflammatory cytokine, up-regulation of gene expression by tobacco smoke, and higher serum levels for smokers and for asthmatics were reported. IL6 single nucleotide polymorphisms (SNPs) were associated with changes in lung function parameters and asthma. Objective To assess interactions of IL6 SNPs and SHS on the risk of adult-onset asthma. Methods A population-based incident case-control study of clinically defined adult-onset asthma and random controls, among adults 21 to 63 years old in Finland. Six tagging SNPs were genotyped. Among non-smokers, genotyping was available for 217 cases and 316 disease-free controls. Results Rs2069827 genotype AA, rs1800797 genotype GA, and rs2069861 genotype AG had synergistic effect with recent SHS exposure. Carriage of any one of them had synergistic effect with SHS, so that the relative excess risk due to interaction (RERI) was 2.22, 95% confidence interval 0.67-5.27, and carriage of any two had even higher synergism (RERI 7.83, -0.02-79.68). In a haplotype analysis of the same SNPs, carriage of haplotype H4 (CAA) or H6 (AAG) (except for a protective haplotype pair H3/H6) was found to show synergism with SHS, RERI 3.05 (-0.66-15.46) and 2.19 (-0.20-8.70), respectively. For of H4 and H6 carriers combined, a synergistic effect was again seen (RERI 3.43, 0.76-10.03). Conclusions IL6 SNPs and SHS have synergistic effect on the risk of adult-onset asthma, carriage of several risk genotypes or a risk haplotype is associated with higher synergistic effect.
- © 2014 ERS
