Open AccessPolymorphism −116 C / G of Human X ‐box‐Binding Protein 1 Promoter is Associated with Risk of A lzheimer's Disease
Author(s) -
Liu ShengYuan,
Wang Wei,
Cai ZhiYou,
Yao LiFen,
Chen ZhongWei,
Wang ChangYi,
Zhao Bin,
Li KeShen
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12064
Subject(s) - xbp1 , genotype , endoplasmic reticulum , allele , medicine , pathogenesis , microbiology and biotechnology , biology , endocrinology , genetics , gene , rna splicing , rna
Summary Aim A lzheimer's disease ( AD ) is a multifactor disease that has been reported to have a close association with endoplasmic reticulum ( ER ) stress response. In the response, the regulator factor human X ‐box‐binding protein 1 ( XBP 1) has been shown to facilitate the refolding and degradation of misfolded proteins, prevent neurotoxicity of amyloid‐beta ( A β) and tau, and play an important role in the survival of neurons. The aim in the study was to analyze the potential association between the −116 C / G polymorphism of XBP1 and the risk of AD . Methods The association between −116 C / G polymorphism of XBP1 promoter and possible risk of AD was assessed among 276 patients with AD and 254 matched healthy individuals in a case–control study. Results Overall, there was a significantly statistical difference in genotype ( P = 0.0354) and allele frequencies ( P = 0.0150, OR = 1.3642, 95% CI = 1.0618–1.7528) between the AD subjects and control subjects, showing that the −116 C / G polymorphism of XBP1 might lead to increased susceptibility for AD in a C hinese H an population. In addition, the −116 CG and −116 GG genotypes were significantly associated with increased AD risk in female ( P = 0.0217) and in subjects with APOE є4 (−) ( P = 0.0070) in stratified analyses, and the −116 CC genotype was significantly associated with fast cognitive deterioration in the AD patients ( P = 0.0270). Conclusion The study supports a role for the −116C/G polymorphism of XBP1 gene in the pathogenesis of AD , and further studies with a larger sample size and detailed data should be performed in other populations.