Genetic variation in BDNF is associated with allergic asthma and allergic rhinitis in an ethnic Chinese population in Singapore
Genetic variation in BDNF is associated with allergic asthma and allergic rhinitis in an ethnic Chinese population in Singapore
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DOI：
10.1016/j.cyto.2011.05.008
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发表时间：
2011-11-01
期刊：
影响因子：
3.8
通讯作者：
Chew, Fook Tim
中科院分区：
文献类型：
--
作者：
Andiappan, Anand Kumar;Parate, Pallavi Nilkanth;Chew, Fook Tim
过敏性疾病影响世界人口的25%以上，是遗传和环境因素之间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）可以作为过敏性疾病的重要标志。在变应性鼻炎（AR）、哮喘和特应性湿疹患者中，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性和严重程度呈正相关。然而，关于BDNF基因变异与过敏性疾病之间关系的报道一直存在争议。因此，本研究旨在阐明新加坡华人BDNF单核苷酸多态性（snp）与AR和哮喘遗传易感性之间的关系。本研究中使用的志愿者有自我报告的哮喘史（718名受试者）或由研究人员管理的问卷确定的AR史（795名受试者），同时对照组没有个人或家族过敏史（717名受试者）。关联结果发现标签snp rs10767664与AR显著相关，AR显著P-Dominant = 0.0007, OR = 1.3，哮喘显著P-Dominant = 0.0005, OR = 1.3（使用显性关联模型）。基于单倍型的分析也发现了一个显著的关联，进一步证实了单SNP的关联。SNP rs 10767664与功能多态性rs6265 （Va166Met）密切相关（r(2) = 0.95），该多态性先前被报道与过敏表型相关，也显示影响BDNF表达。因此，BDNF是过敏的关键分子。对BDNF多态性的进一步研究可能揭示其在变态反应性疾病发病机制中的作用，并可能作为变态反应性疾病的生物标志物。(C) 2011 Elsevier Ltd.版权所有。
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, broncho-alveolar 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 P-Dominant = 0.0007 and OR = 1.3 for AR and P-Dominant = 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 rs 10767664 is strongly linked (r(2) = 0.95) to the functional polymorphism rs6265 (Va166Met), 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. (C) 2011 Elsevier Ltd. All rights reserved.