Department of Biological Sciences, National University of Singapore, Science Drive 4, Singapore 117543, Singapore.
Cytokine. 2011 Nov;56(2):218-23. doi: 10.1016/j.cyto.2011.05.008. Epub 2011 Jun 30.
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 disease.
变应性疾病影响全球超过 25%的人口,是遗传和环境因素复杂相互作用的结果。最近的证据表明,BDNF(脑源性神经营养因子)可以作为变应性疾病的一个重要标志物。过敏性鼻炎(AR)、哮喘和特应性皮炎患者血液、支气管肺泡灌洗液和鼻灌洗液中 BDNF 水平升高与疾病活动度和严重程度呈正相关。然而,关于 BDNF 基因变异与变应性疾病之间的关联的报告存在争议。因此,本研究旨在阐明新加坡华人中 BDNF 单核苷酸多态性(SNP)与 AR 和哮喘遗传易感性的关系。本研究使用了自报哮喘史(718 例)或研究者管理问卷确定的 AR 史(795 例)的志愿者,以及无过敏个人或家族史的对照(717 例)。关联结果确定了标签 SNP rs10767664 与 AR 有显著关联(PDominant=0.0007,OR=1.3),与哮喘有显著关联(PDominant=0.0005,OR=1.3)(采用关联的显性模型)。基于单倍型的分析也确定了一个显著的关联,进一步证实了单 SNP 关联。SNP rs10767664 与功能多态性 rs6265(Val66Met)密切相关(r2=0.95),后者先前已被报道与变应性表型相关,并且也被证明影响 BDNF 表达。BDNF 因此是过敏的关键分子参与者。进一步研究 BDNF 内的多态性可能阐明其在变应性疾病发病机制中的作用,并可能作为变应性疾病的生物标志物。