Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study.
dc.contributor.author | Kulminski, Alexander M | |
dc.contributor.author | Raghavachari, Nalini | |
dc.contributor.author | Arbeev, Konstantin G | |
dc.contributor.author | Culminskaya, Irina | |
dc.contributor.author | Arbeeva, Liubov | |
dc.contributor.author | Wu, Deqing | |
dc.contributor.author | Ukraintseva, Svetlana V | |
dc.contributor.author | Christensen, Kaare | |
dc.contributor.author | Yashin, Anatoliy I | |
dc.coverage.spatial | Netherlands | |
dc.date.accessioned | 2017-06-02T17:28:15Z | |
dc.date.available | 2017-06-02T17:28:15Z | |
dc.date.issued | 2016-11 | |
dc.description.abstract | The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Family Study, and intermediate mechanisms, which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis detected favorable associations of the ε2 allele with lower LDL-C levels, lower risks of HD, and better survival. The ε2 allele was associated with LDL-C in each gender and biodemographic cohort, including long-living individuals, offspring, and spouses, resulting in highly significant association in the entire sample (β = -7.1, p = 6.6 × 10(-44)). This allele was significantly associated with HD in long-living individuals and offspring (relative risk [RR] = 0.60, p = 3.1 × 10(-6)) but this association was not mediated by LDL-C. The protective effect on survival was specific for long-living women but it was not explained by LDL-C and HD in the adjusted model (RR = 0.70, p = 2.1 × 10(-2)). These results show that ε2 allele may favorably influence LDL-C, HD, and survival through three mechanisms. Two of them (HD- and survival-related) are pronounced in the long-living parents and their offspring; the survival-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking ε2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care and personalized medicine. | |
dc.identifier | ||
dc.identifier | 10.1007/s10522-016-9659-3 | |
dc.identifier.eissn | 1573-6768 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartof | Biogerontology | |
dc.relation.isversionof | 10.1007/s10522-016-9659-3 | |
dc.subject | ApoE | |
dc.subject | Health span | |
dc.subject | Life span | |
dc.title | Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study. | |
dc.type | Journal article | |
duke.contributor.orcid | Arbeev, Konstantin G|0000-0002-4195-7832 | |
pubs.author-url | ||
pubs.begin-page | 893 | |
pubs.end-page | 905 | |
pubs.issue | 5-6 | |
pubs.organisational-group | Center for Population Health & Aging | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Duke Population Research Institute | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.organisational-group | Sanford School of Public Policy | |
pubs.organisational-group | Social Science Research Institute | |
pubs.organisational-group | Staff | |
pubs.organisational-group | University Institutes and Centers | |
pubs.publication-status | Published | |
pubs.volume | 17 |
Files
Original bundle
- Name:
- Protective role of the apolipoprotein E2 allele in age-related.pdf
- Size:
- 458.59 KB
- Format:
- Adobe Portable Document Format