| The role of lipid-related genes, aging-related processes, and environment in healthspan. | |
| | |
MedLine Citation:
|
PMID: 23320904 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The inherent complexity of aging-related traits can temper progress in unraveling the genetic origins of healthspan. We focus on two generations in the Framingham Heart Study, the original (FHS) and offspring (FHSO) cohorts, to determine whether aging-related processes in changing environments can substantially impact the role of lipid-related genes discovered in candidate-gene (the apolipoprotein E (APOE) e2/3/4 polymorphism) and genome-wide (the APOB rs1042034 (C/T)) studies, in regulation of total cholesterol (TC) and onset of cardiovascular disease (CVD). We demonstrate that the APOE e4 allele and APOB CC genotype can play detrimental, neutral, and protective sex-specific roles in the etiology of CVD at different ages and in different environments. We document antagonistic roles for the e4 allele in the onset of CVD characterized by detrimental effects at younger ages (RR(≤75yrs) =1.49, p=7.5×10(-4) ) and protective effects at older ages (RR(76+yrs) =0.77, p=0.044) for FHS participants. We found that disregarding the role of aging erroneously nullifies the significant effects of the e4 allele in this sample (RR=0.92, p=0.387). The leading bio-genetic pathways mediating genetic effects on CVD may be more relevant to lipid metabolism for APOB than APOE. Aging-related processes can modulate the strength of genetic associations with TC in the same individuals at different chronological ages. We found substantial differences in the effects of the same APOE and APOB alleles on CVD and TC across generations. The results suggest that aging-related processes in changing environments may play key roles in the genetics of healthspan. Detailed systemic integrative analyses may substantially advance the progress. © 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
| | |
Authors:
|
Alexander M Kulminski; Irina Culminskaya; Konstantin G Arbeev; Svetlana V Ukraintseva; Eric Stallard; Liubov Arbeeva; Anatoli I Yashin |
Related Documents
:
|
23514664 - Fatal and non-fatal injuries due to intentional explosions in nepal, 2008-2011: analysi... 22193574 - Secondhand smoke exposure and hair nicotine in children: age-dependent differences. 23316414 - Factors influencing quality of life in caregivers of people with parkinson's disease an... 23448034 - Reproductive traits of glenea cantor (coleoptera: cerambycidae: lamiinae). 3821114 - Gender roles and female drinking-driving. 3594314 - Participation motivation of australian children involved in organized sport. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-16 |
Journal Detail:
|
Title: Aging cell Volume: - ISSN: 1474-9726 ISO Abbreviation: Aging Cell Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
© 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
Affiliation:
|
Center for Population Health and Aging, Duke University, Trent Hall, Room 002, Box 90408, Durham, NC, 27708, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Optimal schedule of adjuvant chemotherapy with S-1 for stage III colon cancer: study protocol for a ...
Next Document: Rapeseed and its Products-Sources of Bioactive Compounds: A Review of their Characteristics and Anal...