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Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis.

ABSTRACT: Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP).Case control study.Buccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression.The frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-alpha (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86; confidence interval, 1.4-3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups.TNF-alpha-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-alpha is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases.

SUBMITTER: Bernstein JM

PROVIDER: S-EPMC2952427 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis.

Bernstein Joel M JM Anon Jack B JB Rontal Michael M Conroy Jeffrey J Wang Chong C Sucheston Lara L

The Laryngoscope 20090701 7

<h4>Objectives/hypothesis</h4>Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP).<h4> ...[more]

PMID: 19405090

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Project description:BackgroundRecent literature has indicated the feasibility of microarray analysis in the characterization of chronic sinusitis. We hypothesized that previously unexplored inflammatory mechanisms would be involved in the pathophysiology of noneosinophilic chronic rhinosinusitis with nasal polyps (NE-CRSwNP) and that this technology could be used to identify the gene expression of these novel and previously known mediators.MethodsPatients with CRSwNP failing medical therapy were prospectively enrolled and NP tissue was removed at time of surgery. NE-CRSwNP was diagnosed based on clinical parameters including absence of allergic disease and confirmed with histopathology showing lack of eosinophilic infiltration. Messenger RNA (mRNA) transcripts extracted from study and control patients were then subjected to microarray analysis using Affymatrix based chips. Validation of findings was then confirmed via quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsMicroarray analysis revealed activation of pathways involved in antigen presentation, cellular movement, hematopoiesis, carcinogenesis, apoptosis, and cell signaling. Previously unexplored genes of interest were identified and their differential regulation was validated via qRT-PCR. Our data showed up-regulation of innate inflammation genes (IL-6, IL-8, and monocyte chemoattractant protein 1), hypoxia-induced inflammation 1alpha, and fibrosis (tenascin) and lack of up-regulation of genes associated with allergic, eosinophilic inflammation (IL-4 and IL-13). Additionally, the genes for CXCL1 and autocrine motility factor receptor were novelly identified to be up-regulated.ConclusionThis study explores the utility of gene microarray technology in identifying unexplored targets of immune dysregulation in NE-CRSwNP. Furthermore, the data characterize the immunologic profile of NE-CRSwNP as it differs from other forms of CRSwNP, in particular, those known to be associated with eosinophilic inflammation.

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Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis.

Publications

Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis.

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