Genetic variation in BDNF is associated with allergic asthma and allergic rhinitis in an ethnic Chinese population in Singapore

► We performed a genetic association study of BDNF SNPs to asthma and AR in a large population size of 1893 ethnic Chinese. ► The study with 795 AR cases, 718 asthma cases and 717 no allergy controls was well designed at 98% power for both AR and asthma. ► There was a positive association identified even after correcting for multiple testing which confirmed its role in allergy. ► Negative results for association by Szczepankiewicz et al., (2008) and Hoffjan et al., (2009) were probably due to insufficient power. ► Our study reemphasizes the focus of studying genetic variants in this gene in relation to allergic phenotypes in other populations as well. Allergic diseases affect more than 25% of the world population and result from a complex interplay between genetic and environmental factors. Recent evidence has shown that BDNF (Brain Derived Neurotrophic Factor) could serve as an important marker of allergic disease. Increased levels of BDNF in blood, bronchoalveolar lavage fluid and nasal lavage fluid positively correlate with disease activity and severity in patients with allergic rhinitis (AR), asthma and atopic eczema. However, reports on the association between genetic variation in BDNF and allergic disease have been controversial. This study therefore aims to clarify the relationship between single nucleotide polymorphisms (SNPs) in BDNF and a genetic predisposition to AR and asthma in an ethnic Chinese population of Singapore. Volunteers with a self-reported history of asthma (718 subjects) or a history of AR as determined by a researcher-administered questionnaire (795 subjects) were used in this study, alongside controls with no personal or family history of allergy (717 subjects). The association results identified a significant association for the tagSNP rs10767664 with a significant PDominant=0.0007 and OR=1.3 for AR and PDominant=0.0005 and OR=1.3 for asthma (using a dominant model of association). The haplotype based analysis also identified a significant association further confirming the single SNP association. The SNP rs10767664 is strongly linked (r2=0.95) to the functional polymorphism rs6265 (Val66Met), which has previously been reported to be associated to allergic phenotypes and also shown to affect BDNF expression. BDNF is a therefore a key molecular player in allergy. Further studies on polymorphisms within BDNF may shed light on its role in the pathogenesis of allergic diseases and potentially serve as biomarkers for allergic diseas