The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

Ramcés Falfán-Valencia,Gandhi F Pavón-Romero,Angel Camarena,María Cristina Negrete-García,María De La Luz García,Gustavo Galicia-Negrete,Luis Manuel Teran

doi:10.1155/2012/741313

Abstract

Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17–7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

Highlights

Aspirin-exacerbated respiratory disease (AERD) is a syndrome characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity, as described in 1922 by SzcZeklik et al [1, 2]
Genetic data for the SNPs included in this study are shown in Table 1; minor allele frequency (MAF) of the polymorphisms tested in healthy control subjects had a similar distribution to that reported in international databases (Table 1)
In addition to alterations in the metabolism of arachidonic acid, several proinflammatory cytokines have been associated with AERD

Summary

Introduction

Aspirin-exacerbated respiratory disease (AERD) is a syndrome characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity, as described in 1922 by SzcZeklik et al [1, 2]. The mechanisms underlying aspirin intolerance are not fully defined, with current research focusing on cyclooxygenase 1 (COX-1) inhibition by aspirin and other NSAIDs diverting arachidonic acid metabolism from COX pathways to the lipoxygenase (LO) pathway This leads to increased synthesis of the cysteinylleukotrienes (LT), LTC4, LTD4, and LTE4, resulting in bronchoconstriction, mucus hypersecretion, and possibly the development of polyps and urticaria [1]. The biological plausibility of this hypothesis fact has led to the search for polymorphisms in genes responsible for LT synthesis, to explore associations between these polymorphisms and local tissue levels of the proteins. Other factors such as polymorphisms in the genes for proinflammatory cytokines including TNF, IL1B, IL6, and IL8 are involved in chronic inflammatory and autoimmune diseases. Interleukin 1 (IL-1) is a cytokine associated with inflammatory responses and found in two forms, IL-1α (produced by the IL1A gene) and IL-1β (IL1B), with both

Methods

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Conclusion