A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis

Peng Jin, Anand Kumar Andiappan, Jia Min Quek, Bernett Lee, Bijin Au, Yang Yie Sio, Astrid Irwanto, Claudia Schurmann, Hans Joergen Grabe, Bani Kaur Suri, Sri Anusha Matta, Harm-Jan Westra, Lude Franke, Tonu Esko, Liangdan Sun, Xuejun Zhang, Hong Liu, Furen Zhang, Anis Larbi, Xin XuMichael Poidinger, Jianjun Liu, Fook Tim Chew, Olaf Rotzschke, Li Shi, De Yun Wang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Background: Brain-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.

Objective: We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR.

Methods: Tagging 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 determined by using both in vitro and ex vivo assays.

Results: The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P = .0017; odds ratio, 1.324) and Shandong Chinese populations (P = .039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 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.

Conclusion: A 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.

Original languageEnglish
Pages (from-to)1486-1493.e8
Number of pages16
JournalJournal of Allergy and Clinical Immunology
Volume135
Issue number6
DOIs
Publication statusPublished - Jun-2015

Keywords

  • Brain-derived neurotrophic factor
  • moderate-to-severe allergic rhinitis
  • Singapore Chinese
  • neurotrophins
  • genetic association
  • ACTIVITY-DEPENDENT SECRETION
  • ATOPIC-DERMATITIS
  • PRODUCE NEUROTROPHINS
  • ASSOCIATION ANALYSIS
  • AIRWAY INFLAMMATION
  • CHINESE POPULATION
  • EPITHELIAL-CELLS
  • ASTHMA
  • DISEASES
  • EOSINOPHILS

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