title: Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  Case control study.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA. jbernste@buffalo.edu
authors.forename: Joel M
authors.initials: JM
authors.lastname: Bernstein
authors.forename: Jack B
authors.initials: JB
authors.lastname: Anon
authors.forename: Michael
authors.initials: M
authors.lastname: Rontal
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Conroy
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Lara
authors.initials: L
authors.lastname: Sucheston
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012852:Sinusitis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha