Polymorphism −116C/G of Human X‐box‐Binding Protein 1 Promoter is Associated with Risk of Alzheimer's Disease

• Published in: CNS neuroscience & therapeutics Vol. 19; no. 4; pp. 229 - 234
• Main Authors: Liu, Sheng‐Yuan, Wang, Wei, Cai, Zhi‐You, Yao, Li‐Fen, Chen, Zhong‐Wei, Wang, Chang‐Yi, Zhao, Bin, Li, Ke‐Shen
• Format: Journal Article
• Language: English
• Published: Oxford Wiley-Blackwell 01.04.2013; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Alzheimer's disease; Biological and medical sciences; Case-Control Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; endoplasmic reticulum; Female; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Original; polymorphism; Polymorphism, Genetic - genetics; Regulatory Factor X Transcription Factors; Risk Factors; stress response; Transcription Factors - genetics; Transcription Factors - physiology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; X-Box Binding Protein 1; XBP1; Human; Nervous system diseases; XBP1; Alzheimer disease; Stress; Cerebral disorder; Binding protein; stress response; Central nervous system disease; Risk factor; Degenerative disease; Alzheimer's disease; endoplasmic reticulum; Polymorphism
• DOI: 10.1111/cns.12064
• ISSN: 1755-5930; 1755-5949

Summary Aim Alzheimer'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 (XBP1) has been shown to facilitate the refolding and degradation of misfolded proteins, prevent neurotoxicity of amyloid‐beta (Aβ) 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 −116C/G polymorphism of XBP1 and the risk of AD. Methods The association between −116C/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 −116C/G polymorphism of XBP1 might lead to increased susceptibility for AD in a Chinese Han population. In addition, the −116CG and −116GG 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 −116CC 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.