IL1B but Not IL8 Polymorphisms Are Increased in Aspirin Exacerbated Respiratory Disease Patients Versus Aspirin Tolerant Asthmatics

Background: Aspirin exacerbated respiratory disease (AERD) is a syndrome characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma and aspirin sensitivity. The mechanisms by which produce these manifestations of intolerance are not fully defined, the current research involve alterations in the metabolism of arachidonic acid, cyclooxygenase 1 (COX-1) inhibition and its deviation from substrate to the lipoxygenase (LO) pathway, inducing increased synthesis of leukotrienes (LT). Biological plausibility of this fact has led to the search for polymorphisms in genes responsible for LT synthesis however others factors such as genetics polymorphisms in pro-inflammatory cytokines like, IL1B and IL8 could be associated.

Methods: 78 patients with AERD, 135 aspirin-tolerant asthma (ATA) and 134 healthy control subjects participated. All participants who underwent a simple spirometry, methacholine challenge and nasal challenge with Lysine-aspirin (L-ASA), both tests performed according to international guidelines. Peripheral blood was drawn by venipuncture, genomic DNA was obtained using the commercial BDtract DNA isolation kit. We selected two polymorphisms in two genes related to chronic inflammation rs16944 in IL1B, and rs4073 in IL8, Allelic discrimination of SNPs was performed by Real Time PCR (PCR-RT) on a 7300 Real Time PCR Systems. Statistical analysis was performed between groups of cases (AERD and ATA) vs control group with Epi-info v.6.04 by χ2 test to identify the difference between the allele and genotype frequencies of each polymorphism made, considering a significant p value <0.05, in addition to the calculation of odds ratios and confidence intervals of 95%.

Results: We find no association between IL1B (rs16944) to GG and GA genotypes in ATA patients vs control group neither AERD vs control group. Interestingly, the AA genotype showed increased frequency in the AERD patients vs the ATA patients (FG = 0.19 vs. 0.07), this association remained significant (p =0.018, OR 2.98, CI 1.17-7.82).

Conclusions: This is the first observation that IL1B polymorphisms is involved in AERD, suggest that patients carrying out the IL1B-511 polymorphism (rs16944 AA genotype) may show enhanced susceptibility to develop AERD.