2026-06-30T02:01:16Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/55192024-10-31T11:40:26Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Ma, Yiyi
author
Smith, Caren E.
author
Lai, Chao-Qiang
author
Irvin, Marguerite R.
author
Parnell, Laurence D.
author
Lee, Yu-Chi
author
Pham, Lucia
author
Aslibekyan, Stella
author
Claas, Steven A.
author
Tsai, Michael Y.
author
Borecki, Ingrid B.
author
Kabagambe, Edmond K.
author
Berciano, Silvia
author
Ordovas, Jose M
author
Absher, Devin M
author
Arnett, Donna K
funder
NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos)
funder
NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos)
funder
United States Department of Agriculture
2017-12-01T07:37:26Z
2017-12-01T07:37:26Z
2015
Aging Cell. 2015; 14(1):49-59
10.1111/acel.12293
1474-9726
1474-9718
Aging Cell
25476875
http://hdl.handle.net/20.500.12105/5519
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.
eng
apolipoprotein E
age
DNA methylation
Variants
Epidemiology
Interaction
CORONARY-HEART-DISEASE
APOLIPOPROTEIN-E GENE
DNA METHYLATION
ALZHEIMERS-DISEASE
MONOZYGOTIC TWINS
CPG SITES
POLYMORPHISM
PROMOTER
GENOME
ASSOCIATION
Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study
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