Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved]
Background: The APOE gene encodes apolipoprotein ε (ApoE), a protein that associates with lipids to form lipoproteins that package and traffic cholesterol and lipids through the bloodstream. There are at least three different alleles of the APOE gene: APOE2, APOE3, and APOE4. The APOE4 allele increa...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2019-07-01
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| Series: | F1000Research |
| Online Access: | https://f1000research.com/articles/8-387/v2 |
| _version_ | 1828769682210947072 |
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| author | Michelle Hsu Mehek Dedhia Wim E Crusio Anna Delprato |
| author_facet | Michelle Hsu Mehek Dedhia Wim E Crusio Anna Delprato |
| author_sort | Michelle Hsu |
| collection | DOAJ |
| description | Background: The APOE gene encodes apolipoprotein ε (ApoE), a protein that associates with lipids to form lipoproteins that package and traffic cholesterol and lipids through the bloodstream. There are at least three different alleles of the APOE gene: APOE2, APOE3, and APOE4. The APOE4 allele increases an individual's risk for developing late-onset Alzheimer disease (AD) in a dose-dependent manner. Sex differences have been reported for AD susceptibility, age of onset, and symptom progression, with females being more affected than males. Methods: In this study, we use a systems biology approach to examine gene expression patterns in the brains of aged female and male individuals who are positive for the APOE4 allele in order to identify possible sex-related differences that may be relevant to AD. Results: Based on correlation analysis, we identified a large number of genes with an expression pattern similar to that of APOE in APOE4-positive individuals. The number of these genes was much higher in APOE4-positive females than in APOE4-positive males, who in turn had more of such genes than APOE4-negative control groups. Our findings also indicate a significant sex* genotype interaction for the CNTNAP2 gene, a member of the neurexin family and a significant interaction for brain area*sex* genotype for PSEN2, a risk factor gene for AD. Conclusions: Profiling of these genes using Gene Ontology (GO) term classification, pathway enrichment, and differential expression analysis supports the idea of a transcriptional role of APOE with respect to sex differences and AD. |
| first_indexed | 2024-12-11T13:52:29Z |
| format | Article |
| id | doaj.art-55e213d9288249e38f9f8458ec9c949b |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-11T13:52:29Z |
| publishDate | 2019-07-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-55e213d9288249e38f9f8458ec9c949b2022-12-22T01:04:12ZengF1000 Research LtdF1000Research2046-14022019-07-01810.12688/f1000research.18671.221927Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved]Michelle Hsu0Mehek Dedhia1Wim E Crusio2Anna Delprato3Department of Research and Education, BioScience Project, Wakefield, MA, 01880, USADepartment of Research and Education, BioScience Project, Wakefield, MA, 01880, USAInstitut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR, CNRS and University of Bordeaux, UMR 5287, Pessac cedex, Aquitaine, 33615, FranceDepartment of Research and Education, BioScience Project, Wakefield, MA, 01880, USABackground: The APOE gene encodes apolipoprotein ε (ApoE), a protein that associates with lipids to form lipoproteins that package and traffic cholesterol and lipids through the bloodstream. There are at least three different alleles of the APOE gene: APOE2, APOE3, and APOE4. The APOE4 allele increases an individual's risk for developing late-onset Alzheimer disease (AD) in a dose-dependent manner. Sex differences have been reported for AD susceptibility, age of onset, and symptom progression, with females being more affected than males. Methods: In this study, we use a systems biology approach to examine gene expression patterns in the brains of aged female and male individuals who are positive for the APOE4 allele in order to identify possible sex-related differences that may be relevant to AD. Results: Based on correlation analysis, we identified a large number of genes with an expression pattern similar to that of APOE in APOE4-positive individuals. The number of these genes was much higher in APOE4-positive females than in APOE4-positive males, who in turn had more of such genes than APOE4-negative control groups. Our findings also indicate a significant sex* genotype interaction for the CNTNAP2 gene, a member of the neurexin family and a significant interaction for brain area*sex* genotype for PSEN2, a risk factor gene for AD. Conclusions: Profiling of these genes using Gene Ontology (GO) term classification, pathway enrichment, and differential expression analysis supports the idea of a transcriptional role of APOE with respect to sex differences and AD.https://f1000research.com/articles/8-387/v2 |
| spellingShingle | Michelle Hsu Mehek Dedhia Wim E Crusio Anna Delprato Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved] F1000Research |
| title | Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved] |
| title_full | Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved] |
| title_fullStr | Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved] |
| title_full_unstemmed | Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved] |
| title_short | Sex differences in gene expression patterns associated with the APOE4 allele [version 2; peer review: 2 approved] |
| title_sort | sex differences in gene expression patterns associated with the apoe4 allele version 2 peer review 2 approved |
| url | https://f1000research.com/articles/8-387/v2 |
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