• Peng Jin, Anand Kumar Andiappan, Jia Min Quek, Bernett Lee, Bijin Au, Yang Yie Sio, Astrid Irwanto, Claudia Schurmann, Hans Jörgen 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 Xu, Michael Poidinger, Jianjun Liu, Fook Tim Chew, Olaf Rotzschke, Li Shi, and De Yun Wang.
• Key Laboratory of Otolaryngology of the Ministry of Health, Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, China; Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
• J. Allergy Clin. Immunol. 2015 Jun 1; 135 (6): 1486-93.e8.

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.ObjectiveWe 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 determined by using both in vitro and ex vivo assays.ResultsThe 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.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.Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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