title: Genetic polymorphisms of nerve growth factor receptor (NGFR) and the risk of Alzheimer's disease.
abstract: BACKGROUND
  Loss of basal forebrain cholinergic neurons is attributable to the proapoptotic signaling induced by nerve growth factor receptor (NGFR) and may link to Alzheimer's disease (AD) risk. Only one study has investigated the association between NGFR polymorphisms and the risk of AD in an Italian population. Type 2 diabetes mellitus (DM) may modify this association based on previous animal and epidemiologic studies.
  
  
  METHODS
  This was a case-control study in a Chinese population. A total of 264 AD patients were recruited from three teaching hospitals between 2007 to 2010; 389 controls were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency≥5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from NGFR to test the association between NGFR htSNPs and the risk of AD.
  
  
  RESULTS
  Variant NGFR rs734194 was significantly associated with a decreased risk of AD [GG vs. TT copies: adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.20-0.95]. Seven common haplotypes were identified. Minor haplotype GCGCG was significantly associated with a decreased risk of AD (2 vs. 0 copies: adjusted OR = 0.39, 95% CI = 0.17-0.91). Type 2 DM significantly modified the association between rs2072446, rs741072, and haplotype GCTTG and GTTCG on the risk of AD among ApoE ε4 non-carriers (P(interaction) < 0.05).
  
  
  CONCLUSIONS
  Inherited polymorphisms of NGFR were associated with the risk of AD; results were not significant after correction for multiple tests. This association was further modified by the status of type 2 DM.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Cheng
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Liang-Chuan
authors.initials: LC
authors.lastname: Lai
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Lee
authors.forename: Jen-Hau
authors.initials: JH
authors.lastname: Chen
authors.forename: Ta-Fu
authors.initials: TF
authors.lastname: Chen
authors.forename: Hua-Hsiang
authors.initials: HH
authors.lastname: Chen
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wen
authors.forename: Ping-Keung
authors.initials: PK
authors.lastname: Yip
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Chu
authors.forename: Wei J
authors.initials: WJ
authors.lastname: Chen
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D012307:Risk Factors; D014652:Vascular Diseases / Q000150:complications / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor