Publication: Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study
dc.contributor.author | Ma, Yiyi | |
dc.contributor.author | Smith, Caren E. | |
dc.contributor.author | Lai, Chao-Qiang | |
dc.contributor.author | Irvin, Marguerite R. | |
dc.contributor.author | Parnell, Laurence D. | |
dc.contributor.author | Lee, Yu-Chi | |
dc.contributor.author | Pham, Lucia | |
dc.contributor.author | Aslibekyan, Stella | |
dc.contributor.author | Claas, Steven A. | |
dc.contributor.author | Tsai, Michael Y. | |
dc.contributor.author | Borecki, Ingrid B. | |
dc.contributor.author | Kabagambe, Edmond K. | |
dc.contributor.author | Berciano, Silvia | |
dc.contributor.author | Ordovas, Jose M | |
dc.contributor.author | Absher, Devin M | |
dc.contributor.author | Arnett, Donna K | |
dc.contributor.funder | NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos) | |
dc.contributor.funder | NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos) | |
dc.contributor.funder | United States Department of Agriculture | |
dc.date.accessioned | 2017-12-01T07:37:26Z | |
dc.date.available | 2017-12-01T07:37:26Z | |
dc.date.issued | 2015 | |
dc.description.abstract | Although apolipoprotein E (APOE) variants are associated with age-related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87years) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and from Encyclopedia of DNA Elements (ENCODE) consortium, combined with published methylation datasets, we described the methylation pattern of 13 CpG sites within APOE locus, their correlations with gene expression across cell types, and their relationships with age, plasma lipids, and sequence variants. Based on methylation levels and the genetic regions, we categorized the 13 APOE CpG sites into three groups: Group 1 showed hypermethylation (>50\%) and were located in the promoter region, Group 2 exhibited hypomethylation (<50\%) and were located in the first two exons and introns, and Group 3 showed hypermethylation (>50\%) and were located in the exon 4. APOE methylation was negatively correlated with gene expression (minimum r=-0.66, P=0.004). APOE methylation was significantly associated with age (minimum P=2.06E-08) and plasma total cholesterol (minimum P=3.53E-03). Finally, APOE methylation patterns differed across APOE epsilon variants (minimum P=3.51E-05) and the promoter variant rs405509 (minimum P=0.01), which further showed a significant interaction with age (P=0.03). These findings suggest that methylation may be a potential mechanistic explanation for APOE functions related to aging and call for further molecular mechanistic studies. | |
dc.description.peerreviewed | SÃ | |
dc.description.sponsorship | This study is funded by National Heart Lung and Blood Institute Grant U01HL072524-04 and 5R01HL1043135-04, and the National Institute of Neurological Disorders and Stroke Grant T32NS054584. C. Smith is supported by K08 HL112845. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer. This material is based upon work supported by the USDA, under agreement No. 58-1950-0-014. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA. | |
dc.format.page | 49-59 | |
dc.format.volume | 14 | |
dc.identifier | ISI:000349096600006 | |
dc.identifier.citation | Aging Cell. 2015; 14(1):49-59 | |
dc.identifier.doi | 10.1111/acel.12293 | |
dc.identifier.e-issn | 1474-9726 | |
dc.identifier.issn | 1474-9718 | |
dc.identifier.journal | Aging Cell | |
dc.identifier.pubmedID | 25476875 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5519 | |
dc.language.iso | eng | |
dc.publisher | Wiley | |
dc.relation.publisherversion | https://doi.org/10.1111/acel.12293 | |
dc.repisalud.institucion | CNIC | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionales | |
dc.rights.accessRights | open access | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | apolipoprotein E | |
dc.subject | age | |
dc.subject | DNA methylation | |
dc.subject | Variants | |
dc.subject | Epidemiology | |
dc.subject | Interaction | |
dc.subject | CORONARY-HEART-DISEASE | |
dc.subject | APOLIPOPROTEIN-E GENE | |
dc.subject | DNA METHYLATION | |
dc.subject | ALZHEIMERS-DISEASE | |
dc.subject | MONOZYGOTIC TWINS | |
dc.subject | CPG SITES | |
dc.subject | POLYMORPHISM | |
dc.subject | PROMOTER | |
dc.subject | GENOME | |
dc.subject | ASSOCIATION | |
dc.title | Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study | |
dc.type | journal article | |
dc.type.hasVersion | VoR | |
dspace.entity.type | Publication |
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