Association study of a functional promoter polymorphism in the XBP1 gene and schizophrenia.

Department of Clinical Neuroscience, Psychiatry Section, R5:00, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.23). 02/2006; 141B(1):71-5. DOI: 10.1002/ajmg.b.30262
Source: PubMed

ABSTRACT A functional promoter polymorphism (-116C/G) of the X-box binding protein 1 gene (XBP1) gene was reported to be associated with schizophrenia in Asian subjects. In a replication attempt, three European case-control samples comprising 2,182 German, Polish, and Swedish subjects, were genotyped for the XBP1 -116C/G polymorphism. Allele and genotype frequencies were compared between schizophrenic patients and control subjects. There were no significant case-control differences in any of the three samples, although in a meta-analysis with previous results comprising 3,612 subjects there was a borderline association between the -116G-containing genotypes and schizophrenia. We conclude that the functional XBP1 gene polymorphism is not of major importance to schizophrenia in the European populations investigated. It cannot be excluded, however, that the XBP1 polymorphism is involved in schizophrenia in other populations or adds minor susceptibility to the disorder.

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    CNS Neuroscience & Therapeutics 02/2013; · 4.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The X-box binding protein 1 (XBP1) is a critical transcription factor in the endoplasmic reticulum stress response, which is essential for the maintenance of cellular homeostasis. Here, we investigated whether the regulatory variant rs2269577 of the XBP1 gene influences clinical outcome in advanced non-small cell lung cancer (NSCLC) patients undergoing platinum-based chemotherapy. PATIENTS AND METHODS: We recruited 663 Chinese patients with advanced NSCLC treated with platinum-based regimens and assessed the association between rs2269577 and clinical outcome. Subsequent functional analyses, including real-time quantitative PCR and dual-luciferase assays, were performed to explore possible molecular mechanisms. RESULTS: The G/G genotype of rs2269577 was significantly associated with severe gastrointestinal toxicity compared with the homozygous C/C genotype (P=0.012, odds ratio=2.755), particularly in the female, performance status 0-1, and adenocarcinoma subgroups. No significant relevance was found between rs2269577 and treatment efficacy. In gastric epithelial cells, in vitro molecular analyses demonstrated that XBP1 mRNA expression levels decreased after treatment with cisplatin and the G allele of rs2269577 weakened the transcriptional activity of the XBP1 promoter. CONCLUSION: This is the first study to evaluate the effect of XBP1 polymorphism on severe chemotherapy-related adverse outcomes in platinum-treated advanced NSCLC patients using both pharmacogenomics and functional molecular analyses.
    Lung cancer (Amsterdam, Netherlands) 03/2013; · 3.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurocognitive deficits are a core feature of schizophrenia. Deficits covering a wide range of functions have been well documented. However there is still a lack of longitudinal studies regarding the development of neurocognitive impairment. The current study examined the effect of time in long-term treated patients with schizophrenia and healthy controls on cognitive functions. A neurocognitive test-battery was administered to 36 patients and 46 controls on two occasions with approximately 4.5 years interval. Patients performed significantly worse on all measures on both occasions. The only significant decline over time was the ability to shift mental set between different rules or categories (measured by Trail Making Test B). This decline was present in both patients and controls. Improvement on attention (tested by Continuous Performance Test) was found in patients only and improvement on verbal learning (tested by Rey Auditory Verbal Learning Test) was found only in controls. Education was significantly related to outcome in patients and age was related to outcome in controls. We conclude that neurocognitive function is relatively stable over 4.5 years in patients with long-term treated schizophrenia, in line with previous scientific research. The authors discuss the impact of age and education and limitations of the study.
    Psychiatry Research 05/2012; · 2.68 Impact Factor