title: A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis.
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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Peng
authors: P
authors: Jin
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore; Department of Biological Sciences, National University of Singapore, Singapore.
authors: Anand Kumar
authors: AK
authors: Andiappan
authors: Department of Biological Sciences, National University of Singapore, Singapore.
authors: Jia Min
authors: JM
authors: Quek
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Bernett
authors: B
authors: Lee
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Bijin
authors: B
authors: Au
authors: Department of Biological Sciences, National University of Singapore, Singapore.
authors: Yang Yie
authors: YY
authors: Sio
authors: the Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Astrid
authors: A
authors: Irwanto
authors: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors: Claudia
authors: C
authors: Schurmann
authors: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS Hospital Stralsund, Greifswald, Germany.
authors: Hans Jörgen
authors: HJ
authors: Grabe
authors: Department of Biological Sciences, National University of Singapore, Singapore.
authors: Bani Kaur
authors: BK
authors: Suri
authors: Department of Biological Sciences, National University of Singapore, Singapore.
authors: Sri Anusha
authors: SA
authors: Matta
authors: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Harm-Jan
authors: HJ
authors: Westra
authors: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Lude
authors: L
authors: Franke
authors: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors: Tonu
authors: T
authors: Esko
authors: Institute of Dermatology and Department of Dermatology at No. 1 Hospital, Anhui Medical University, Hefei, China; State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China; Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China; Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, China.
authors: Liangdan
authors: L
authors: Sun
authors: Institute of Dermatology and Department of Dermatology at No. 1 Hospital, Anhui Medical University, Hefei, China; State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China; Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China; Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, China.
authors: Xuejun
authors: X
authors: Zhang
authors: Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, China; Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China; Shandong Provincial Key Lab for Dermatovenereology, Jinan, China; Shandong Provincial Medical Center for Dermatovenereology, Jinan, China.
authors: Hong
authors: H
authors: Liu
authors: Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, China; Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China; Shandong Provincial Key Lab for Dermatovenereology, Jinan, China; Shandong Provincial Medical Center for Dermatovenereology, Jinan, China.
authors: Furen
authors: F
authors: Zhang
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Anis
authors: A
authors: Larbi
authors: Qingdao Caretaker Otolaryngology, Head & Neck Surgery Hospital, Qingdao, China.
authors: Xin
authors: X
authors: Xu
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Michael
authors: M
authors: Poidinger
authors: the Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Jianjun
authors: J
authors: Liu
authors: Department of Biological Sciences, National University of Singapore, Singapore.
authors: Fook Tim
authors: FT
authors: Chew
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
authors: Olaf
authors: O
authors: Rotzschke
authors: Key Laboratory of Otolaryngology of the Ministry of Health, Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, China. Electronic address: shili126@sina.com.
authors: Li
authors: L
authors: Shi
authors: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore. Electronic address: entwdy@nus.edu.sg.
authors: De Yun
authors: de Y
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D065631:Rhinitis, Allergic / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D012306:Risk; D012720:Severity of Illness Index; D012846:Singapore
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D007073:Immunoglobulin E; C579455:BDNF protein, human
keywords: Brain-derived neurotrophic factor; Singapore Chinese; genetic association; moderate-to-severe allergic rhinitis; neurotrophins