title: Genetic variants associated with neutrophil function in aggressive periodontitis and healthy controls.
abstract: BACKGROUND
  Genetic polymorphisms that influence neutrophil function were proposed as possible risk factors for aggressive periodontitis (AgP). The aim of this study is to test whether a clinical diagnosis and specific genetic variants are associated with neutrophil activity in subjects with AgP and healthy subjects.
  
  
  METHODS
  This study describes the results of neutrophil analyses performed in 40 subjects (20 subjects with AgP and 20 healthy control subjects). Neutrophils were extracted from peripheral blood and analyzed in a masked manner for phagocytosis and oxidative burst by flow cytometry in response to Escherichia coli, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), and Porphyromonas gingivalis. Genomic DNA was extracted and genotyped for the nicotinamide adenine dinucleotide phosphate p22 phagocytic oxidase subunit (p22(phox)) cytochrome b alpha gene (CYBA) C242T, crystallizable gamma fragment (Fcgamma)IIa H/R, and FcgammaIIIb neutrophil antigen (NA)1/NA2 polymorphisms.
  
  
  RESULTS
  Analyses in pairs of white subjects (n = 24) revealed that patients with AgP exhibited a higher oxidative burst in response to E. coli (P = 0.002) and P. gingivalis (P = 0.002) compared to healthy control subjects. The p22(phox) CYBA 242 T allele was associated with an oxidative burst in response to the challenge by two strains of A. actinomycetemcomitans (P = 0.018 and P = 0.046). The FcgammaIIa polymorphism was associated with the phagocytic index of E. coli (P = 0.024).
  
  
  CONCLUSIONS
  This study confirms previous reports of a higher oxidative burst associated with AgP and presented preliminary evidence that genetic factors may influence neutrophil function in patients with AgP and healthy individuals.
authors.affiliation: Periodontology Unit and Division of Clinical Research University College London, Eastman Dental Institute London, UK. l.nibali@eastman.ucl.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Nibali
authors.forename: M
authors.initials: M
authors.lastname: O'Dea
authors.forename: G
authors.initials: G
authors.lastname: Bouma
authors.forename: M
authors.initials: M
authors.lastname: Parkar
authors.forename: A J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: S
authors.initials: S
authors.lastname: Burns
authors.forename: N
authors.initials: N
authors.lastname: Donos
mesh_terms: D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology; D010520:Aggressive Periodontitis / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D000483:Alleles; D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004926:Escherichia coli / Q000502:physiology; D005260:Female; D058851:GPI-Linked Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007519:Isoantigens / Q000235:genetics; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D010587:Phagocytosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016966:Porphyromonas gingivalis / Q000502:physiology; D017452:Receptors, IgG / Q000235:genetics; D016897:Respiratory Burst / Q000235:genetics*
chemical_list: C428200:FCGR3B protein, human; C080568:Fc gamma receptor IIA; D058851:GPI-Linked Proteins; D007519:Isoantigens; D017452:Receptors, IgG; C067704:neutrophil-specific antigen NA1, human; C072753:neutrophil-specific antigen NA2; D019255:NADPH Oxidases; C086986:CYBA protein, human