☆ 4.7 Article

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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2015)

Journal

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Volume 135, Issue 6, Pages 1486-U151

Publisher

MOSBY-ELSEVIER

DOI: 10.1016/j.jaci.2014.12.1870

Keywords

Brain-derived neurotrophic factor; moderate-to-severe allergic rhinitis; Singapore Chinese; neurotrophins; genetic association

Funding

Singapore Immunology Network [SIgN-06-006, SIgN-08-020, SIgN-10-029]
National Medical Research Council of Singapore [NMRC/1150/2008]
Biomedical Research Council, Singapore
Agency for Science, Technology and Research (A*STAR)
Science Development Funding Agency of Shandong Province, China [2010G0020258]
National University of Singapore's Graduate Research Scholarship program

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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.

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Allergic rhinitis in Chinese young adults from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort: Prevalence, patterns, and epidemiology of allergic rhinitis

Qi Yi Ambrose Wong, Jun Jie Lim, Jun Yan Ng, Praneeth Malipeddi, Wei Yi Teo, Yi Ying Eliza Lim, Yu Ting Ng, Yang Yie Sio, Sri Anusha Matta, Yi Ru Wong, Keng Foo Teh, Smyrna Moti Rawanan Shah, Kavita Reginald, Yee How Say, Fook Tim Chew

Summary: This study found an increase in AR prevalence over time in Asia. Factors such as male gender, parental history of allergic diseases increased the risk of AR, while factors like age, housing type, income level, pet ownership, sedentary lifestyle, and dietary habits were associated with AR. The study identified modifiable risk factors such as TV/computer usage and dietary habits that may impact AR manifestation, opening up new avenues for research in gene-environment interactions and AR management.

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