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oai:repisalud.isciii.es:20.500.12105/55192024-10-31T11:40:26Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2015 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. 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 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