scholarly journals Association between clusterin gene polymorphism rs11136000 and late-onset Alzheimer's disease susceptibility: A review and meta-analysis of case-control studies

2016 ◽  
Vol 12 (5) ◽  
pp. 2915-2927 ◽  
Author(s):  
Wenjin Du ◽  
Jiping Tan ◽  
Wei Xu ◽  
Jinwen Chen ◽  
Luning Wang
2020 ◽  
Vol 17 (2) ◽  
pp. 105-111
Author(s):  
Haitao Liu ◽  
Wei Ge ◽  
Wei Chen ◽  
Xue Kong ◽  
Weiming Jian ◽  
...  

Objectives: Previous case-control studies have focused on the relationship between ALDH2 gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented this up-to-date meta-analysis to assess the probable association. Methods: Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical- Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions on language and ethnicity. Results: Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis. Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed. Conclusions: This study comprehends only five existing case-control studies and the result is negative. The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol or cohort studies should be done to enhance the association between ALDH2 polymorphism and AD or other neurodegenerative diseases.


2012 ◽  
Vol 259 (8) ◽  
pp. 1519-1529 ◽  
Author(s):  
Xue Qin ◽  
Qiliu Peng ◽  
Zhiyu Zeng ◽  
Zhiping Chen ◽  
Liwen Lin ◽  
...  

2021 ◽  
Vol 13 ◽  
Author(s):  
Qianwen Wang ◽  
Jingjing Zhao ◽  
Hongtao Chang ◽  
Xu Liu ◽  
Ruixia Zhu

Background: Recent studies have reported that homocysteine (Hcy) may play a vital role in the pathogenesis of vascular dementia (VaD) and Alzheimer's disease (AD). Our study explored the relationship between the plasma Hcy and folate levels and the risk of dementia.Methods: We searched Embase, PubMed, and Web of Science for published literature, including case-control studies and prospective cohort studies, and performed a systematic analysis.Results: The results of our meta-analysis, consisting of case-control studies, showed higher levels of Hcy and lower levels of folate in dementia, AD, and VaD patients than those in non-demented controls (for dementia: SMD = 0.812, 95% CI [0.689, 0.936], p = 0.000 for Hcy; SMD = −0.677, 95% CI [−0.828, −0.525], p = 0.000 for folate). AD patients showed significantly lower plasma Hcy levels compared to VaD patients (SMD = −0.278, 95% CI [−0.466, −0.09], p = 0.000). Subgroup analysis revealed that ethnicity, average age, and dementia type had no significant effect on this association. Furthermore, from the analysis of prospective cohort studies, we identified that elevated plasma Hcy levels were associated with an increased risk of dementia, AD, and VaD (RRdementia = 1.22, 95% CI [1.08, 1.36]; RRAD = 1.07, 95% CI [1.04, 1.11]; RRVaD = 1.13, 95% CI [1.04, 1.23]). In addition, every 5 μmol/L increase in the plasma Hcy level was associated with a 9% increased risk of dementia and a 12% increased risk of AD.Conclusion: Hcy and folic acid are potential predictors of the occurrence and development of AD. A better understanding of their function in dementia could provide evidence for clinicians to rationalize clinical intervention strategies.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ricardo A. Cifuentes ◽  
Juan Murillo-Rojas

There is a controversial relationship between HLA-A2 and Alzheimer’s disease (AD). It has been suggested a modifier effect on the risk that depends on genetic loadings. Thus, the aims of this study were to evaluate this relationship and to reveal genes associated with both concepts the HLA-A gene and AD. Consequently, we did first a classical systematic review and a meta-analysis of case-control studies. Next, by means of an in silico approach, we used experimental knowledge of protein-protein interactions to evaluate the top ranked genes shared by both concepts, previously found through text mining. The meta-analysis did not show a significant pooled OR (1.11, 95% CI: 0.98 to 1.24 in Caucasians), in spite of the fact that four of the included studies had a significant OR > 1 and none of them a significant OR < 1. In contrast, the in silico approach retrieved nonrandomly shared genes by both concepts (P= 0.02), which additionally encode truly interacting proteins. The network of proteins encoded byAPP, ICAM-1, ITGB2, ITGAL, SELP, SELL, IL2, IL1B, CD4, andCD8Alinked immune to neurodegenerative processes and highlighted the potential roles in AD pathogenesis of endothelial regulation, infectious diseases, specific antigen presentation, and HLA-A2 in maintaining synapses.


Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Jian Yi ◽  
Lan Xiao ◽  
Sheng-Qiang Zhou ◽  
Wen-Jiang Zhang ◽  
Bai-Yan Liu

AbstractFolate metabolism makes a crucial contribution towards late-onset Alzheimer’s disease (LOAD). Moreover, methylenetetrahydrofolate reductase (MTHFR) constitutes the primary enzyme of the folate pathway. We hypothesize that there is an association of C677T polymorphism in the MTHFR gene with the susceptibility to LOAD. Previous published research has investigated the link between the MTHFR C677T polymorphisms and LOAD susceptibility; nevertheless, the findings have continued to be not only controversial, but also indecisive. Accordingly, we carried out the present meta-analysis for the assessment of the potential link that exists between the MTHFR C677T polymorphism and the susceptibility to LOAD. Furthermore, we carried out a literature search of the PubMed, EMBASE, Cochrane Library, and WanFang database up to August 10, 2018. The odds ratios (ORs) with the respective 95% confidence interval (95%CI) were put to use for the evaluation of the robustness of the link of the MTHFR C677T polymorphism with the vulnerability to LOAD. All statistical analyses were carried out using STATA 15.0. An aggregate of 14 case-control research works was retrieved, involving 2,467 LOAD patients as well as 2,877 controls. We found that a substantial link exists between C677T polymorphism and LOAD risk in a codominant framework (TC vs. CC: OR=1.22, 95%CI=1.00-1.49, P=0.049). In addition to the stratified analysis based on ethnicity, which suggested that C677T polymorphism was likely linked only to an augmented threat of LOAD in Asians, it did not exist among Caucasians. Furthermore, in the subgroup analysis carried out using APOE ɛ4 status, a substantial increase in the susceptibility to LOAD was detected in APOE ɛ4 carriers as well as non-APOE ɛ4 carriers. In sum, the current meta-analysis revealed that MTHFR C677T polymorphism was associated with susceptibility to LOAD. Further extensive case-control studies are required.


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