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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.    Conclusion  Inherited polymorphisms of the vascular susceptibility gene  NINJ2  were associated with AD risk.

Genetic Polymorphisms of a Novel Vascular Susceptibility Gene, Ninjurin2 (NINJ2), Are Associated with a Decreased Risk of Alzheimer's Disease