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pmid:29224028
ATP Binding Cassette Subfamily A Member 2 (ABCA2) Expression and Methylation are Associated with Alzheimer's Disease.
Wanhua Hu · Xiaodong Lin · Huihe Zhang · Na Zhao
Medical science monitor : international medical journal of experimental and clinical research · 2017 doi:10.12659/msm.905524
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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MATERIAL AND METHODS To explore the diagnosis value of ABCA2 mRNA expression in AD, 2 datasets GES15222 and GSE33000 containing expression profile of brain cortex tissues and 2 datasets GSE63063 (Cohort 1) and GSE63063 (Cohort 2) containing expression profile of blood were downloaded from the NCBI GEO database and analyzed by receiver operating characteristic curve (ROC) analyses and logistic regression. The ABCA2 co-expressed genes were also analyzed by GO annotation to investigate the potential molecular mechanisms. RESULTS The analyses results suggested ABCA2 mRNA expression was upregulated significantly in AD compared with controls in all datasets. ROC analysis suggested that ABCA2 was associated with AD in all datasets, which were also proved by univariate and multivariate analyses. Next, the dataset GSE80970 containing methylation profiles of prefrontal cortex tissues from AD patients were downloaded and analyzed. Methylation of 2 of 36 CpG islands in ABCA2 gene with high diagnostic accuracy of AD from controls in ROC analyses were found to be negatively associated with AD risk in univariate analysis. One was still associated with AD risk after adjustment of confounding factors. Additional analyses indicated that ACBA2 mRNA expression could be used to diagnose mild cognitive impairment (MCI) and Huntington's disease (HD) from controls and to distinguish HD from AD, but not AD from MCI. Furthermore, the genes involved in AD during ABCA2 alteration were analyzed by GO analysis. CONCLUSIONS ABCA2 mRNA expression and methylation is associated AD risk. ABCA2 may be used as a biomarker for AD diagnosis and may be a potential therapeutic target of AD.", "claims": [{"id": "claim-method", "statement": "Receiver operating characteristics (ROC) curves were used to investigate the diagnostic value of ABCA2 in Alzheimer’s (Figure 1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29224028", "locator": "sections[5] \"Association of ABCA2 with clinical features, age, and sex, and risk of Alzheimer’s disease\" paragraph 2", "quote": "Receiver operating characteristics (ROC) curves were used to investigate the diagnostic value of ABCA2 in Alzheimer’s (Figure 1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Four microarray datasets (GES15222 [21], GSE33000 [22], GSE63063 (Cohort 1) [23], and GSE63063 (Cohort 2) [23]) were downloaded from NCBI GEO databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29224028", "locator": "sections[4] \"ABCA2 was upregulated in Alzheimer’s disease\" paragraph 2", "quote": "Four microarray datasets (GES15222 [21], GSE33000 [22], GSE63063 (Cohort 1) [23], and GSE63063 (Cohort 2) [23]) were downloaded from NCBI GEO databases."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:29224028"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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