The BDNF Gene Variant In Allergic Rhinitis And The Histopathological And Immunopathological Features In Antrochoanal Polyps

BackgroundBrain-derived neurotrophic factor(BDNF)is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis(AR),atopic asthma,and eczema,but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR.We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR.MethodsTagging single nucleotide polymorphisms(SNPs)spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing(CHB)data set,and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients(2216 from Shandong province and 1239 living in Singapore).The functional effects of the BDNF genetic variants were determinedby using both in vitro and ex vivo assays.ResultsThe tagging SNP rs 10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese(P = 0.0017;odds ratio,1.324)and Shandong Chinese populations(P = 0.039;odds ratio,1.180),The coding nonsynonymous SNP rs6265 was in perfect linkage with rs 10767664 and conferred increased BDNF protein secretion by a human cell line in vitro.Subjects bearing the AA genotype of rs 10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma.Using a large-scale expression quantitative trait locus study,we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood.ConclusionA common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR,and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood.Together,these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR.BackgroundAlthough macroscopically similar to the classic bilateral nasal polyps(BNP),the pathogenesis and etiology of antrochoanal polyps(ACP)remain unclear.The aim of this study was to characterize the inflammatory cellular infiltration,the epithelial remodeling patterns as well as the immunopathologic profiles in Chinese patients with ACP.MethodsA detailed histological study was performed employing immunohistochemistry.33 ACPs,49 BNPs and 50 healthy subjects used as controls were obtained.The histological patterns and inflammatory cell infiltration were evaluated and analyzed for associations with clinical characteristics.Then levels of mRNA for inflammatory cell and T-cell related markers were detennined by quantitative PCR were analyzed in 21 ACPs and 34 controls.ResultsLess severe epithelial hyperplasia and goblet cell hyperplasia were found in ACP compared to classic NP.In ACP,87.9%of cases demonstrated neutrophilia.Elevated proportions of macrophages and CD8+ T cells,and alleviated infiltration of Mast cells was observed.Eosinophils infiltration was found to be positive related with the history of asthma;macrophages percent was analyzed to have a significantly negative correlation with epithelial hyperplasia and goblet cell hyperplasia;the infiltration of CD8+ T cell and squamous metaplasia were found to have a positive correlation.The expression levels of T-reg genes(FOXP3 and IL10)were significantly higher in ACP than in controls.Significantly increased IL6.neutrophil-related gene(MPO),eosinophil recruitment genes(CCL13 and CCL18)was also observed in ACP than in controls.However,expression levels of Thl/Th2/Th17 transcription factors T-bet,GATA3 and RORc were significantly decreased in ACP vs controls.The expression of FOXP3 was positively correlated with T-bet,GATA3,IL17R and IL12A,while no significant correlation with RORc was evident.IL6 was observed positively correlated with T-bet,GATA3,FOXP3 and IL17R.IL10 had significant correlation with T-bet and IL12A.Moreover,MPO was observed positively correlated with RORc and CCL18,and CCL18 was significantly correlated with IL17R.In ACP tissues,the expression level of IL10 mRNA was positively correlated with macrophage frequency.CCL18 mRNA level was negatively correlated with Foxp3+T-reg frequency.The expression level of MPO mRNA was negatively correlated with both CD4+ T cell count and CD8+ T cell count.A significantly positive correlation was observed between T-bet mRNA level and CD8+ T cell count.A significantly negative correlation was observed between RORc mRNA level and CD4+ T cell count.ConclusionACP involved a complex inflammation with significantly elevated neutrophils,CD8+ T cells and macrophages.However,immune regulation fails to control the underlying tissue pathology.IL6,IL10 and FOXP3 may play important role in the pathogenesis of ACP.Inflammation has potential roles in ACP and ACP may differ in its pathogenesis from classic NP.