ABSTRACT
Abstract Introduction: Chronic rhinosinusitis with nasal polyps is a multifactorial disease with a complex pathophysiology involving multiple genetic and environmental factors. Objective: The purpose of this work review is to focus on the importance of genetic studies in chronic rhinosinusitis with nasal polyps besides the several barriers that exists for its understanding. Methods: A systematic review on studies of association between single nucleotide polymorphisms and chronic rhinosinusitis with nasal polyps based on a PubMed/Medline and Periódicos CAPES search of all articles published between January 2005 and January 2015 was made. The search was guided on studies containing the terms polymorphisms, rhinosinusitis, and polyps. Results: Two studies found an association of MMP-9 and MMP-2 polymorphisms and chronic rhinosinusitis with nasal polyps, but not in patients with recurrent nasal polyps. Other studies found an association of nasal polyps with MMP-9 polymorphisms, but not with MMP-2 ones. There is evidence of an association of LTC4S, NOS2A, PTGDR, MET, COX-2, OSF-2, and LF polymorphisms and the risk of developing nasal polyps, especially when combined with chronic allergic rhinitis and asthma. Conclusion: Genetic studies on chronic rhinosinusitis with nasal polyps are promising and may offer insights into its pathophysiology, which is likely affected by multiple genetic factors.
Resumo Introdução: A rinossinusite crônica com pólipos nasais é uma doença multifatorial com uma fisiopatologia complexa envolvendo múltiplos fatores genéticos e ambientais. Objetivo: O objetivo deste trabalho é enfatizar a importância dos estudos genéticos na rinossinusite crônica com pólipos nasais, além das diversas barreiras existentes para sua compreensão. Método: Realizou-se uma revisão sistemática de estudos de associação entre polimorfismos de nucleotídeo único e rinossinusite crônica com pólipos nasais com base em uma busca feita nos bancos de dados PubMed/Medline e Periódicos CAPES de todos os artigos publicados entre janeiro de 2005 e janeiro de 2015. A busca foi direcionada à estudos contendo os termos polimorfismos, rinossinusite e pólipos. Resultados: Dois estudos encontraram uma associação entre os polimorfismos MMP-9 e MMP-2 e rinossinusite crônica com pólipos nasais, mas não em pacientes com pólipos nasais recorrentes. Outros estudos encontraram uma associação de pólipos nasais com polimorfismos MMP-9, mas não com MMP-2. Existem evidências de uma associação dos polimorfismos LTC4S, NOS2A, PTGDR, MET, COX-2, OSF-2 e LF e o risco de desenvolver pólipos nasais, especialmente quando combinados com rinite alérgica crônica e asma. Conclusão: Estudos genéticos sobre rinossinusite crônica com pólipos nasais são promissores e podem oferecer conhecimento sobre sua fisiopatologia, que é provavelmente afetada por múltiplos fatores genéticos.
Subject(s)
Humans , Male , Female , Sinusitis/genetics , Rhinitis/genetics , Nasal Polyps/genetics , Polymorphism, Single Nucleotide , Asthma/physiopathology , Asthma/genetics , Sinusitis/physiopathology , Rhinitis/physiopathology , Nasal Polyps/physiopathology , Chronic Disease , Risk Factors , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Genetic Association StudiesABSTRACT
IL-8 is one of the pro-inflammatory cytokines which can play an essential role in the pathogenesis of chronic rhinosinusitis [CRS] as well as nasal polyposis [NP]. The ability of individuals in producing IL-8 is partially determined by IL-8-251 A/T polymorphism. Hence, the aim of the present study was to investigate the association between IL-8-251 A/T and CXCR2 +1208 C/T genes polymorphisms and susceptibility to CRS and NP. Two hundred and forty five CRS patients and 204 healthy controls were included in this study. CRS patients were categorized by the existence or absence of NP. IL-8 promoter-251 A/T and CXCR2 +1208 C/T gene polymorphisms were genotyped via the allele specific PCR [AS-PCR] method. While no remarkable difference was demonstrated between patients and controls for both CXCR2 +1208 C/T and IL-8 -251 A/T polymorphisms, a significant increase in IL-8-251 AA genotype was detected in CRS patients with NP compared to those without it [29.3% and 16.2%, respectively; P=0.03]. Interestingly, this association got far stronger when only non-asthmatic CRS patients were taken into consideration [P=0.001]. The results of the present study indicate that the inheritance of IL-8-251 Aallele is associated significantly with NP development in CRS patients. Therefore, NP formation might be a result of the exposure to an intense inflammatory environment, which is more likely in genetically susceptible CRS patients