title: Genetic polymorphisms of a novel vascular susceptibility gene, Ninjurin2 (NINJ2), are associated with a decreased risk of Alzheimer's disease.
abstract: BACKGROUND
  Accumulated evidences have shown that vascular risk factors, e.g., hypertension, diabetes mellitus and hyperlipidemia, may be related to the risk of dementia. This study investigated the association between genetic polymorphisms of a vascular susceptibility gene, Ninjurin2 (NINJ2), and the risk of dementia, which has not been explored previously.
  
  
  METHODS
  A total of 275 Alzheimer's disease (AD) patients and 119 vascular dementia (VaD) patients aged 50 or older were recruited from three teaching hospitals from 2007 to 2010. Healthy controls (n = 423) with the same age of cases were recruited from the health checkup and volunteers worked at the hospital during the same time period. Five common (frequency >5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) in NINJ2 were genotyped to test for the association between sequence variants of NINJ2 and dementia risk, and how vascular risk factors modify this association.
  
  
  RESULTS
  Homozygosity of two NINJ2 SNPs was significantly associated with a decreased risk of AD [rs11833579: adjusted odds ratio (AOR) = 0.43; 95% confidence interval (CI)= 0.23-0.80; rs12425791: AOR= 0.33, 95% CI= 0.12-0.96]. Five common haplotypes (cumulative frequency= 97%) were identified. The global test for the association between NINJ2 haplotypes and AD was significant (p = 0.03). Haplotype CAGGA was significantly associated with a decreased risk of AD (AOR= 0.32, 95% CI= 0.11-0.94). No associations were observed for VaD.
  
  
  CONCLUSIONS
  Inherited polymorphisms of the vascular susceptibility gene NINJ2 were associated with AD risk.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Kun-Pei
authors.initials: KP
authors.lastname: Lin
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Liang-Chuan
authors.initials: LC
authors.lastname: Lai
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Huang
authors.forename: Jen-Hau
authors.initials: JH
authors.lastname: Chen
authors.forename: Ta-Fu
authors.initials: TF
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
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 / Q000235:genetics*; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D015140:Dementia, Vascular / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C504206:NINJ2 protein, human