Evidence map›Paper›PMID 24920721›Full record

ArticleCirculation2014

Epigenome-wide association study of fasting blood lipids in the Genetics of Lipid-lowering Drugs and Diet Network study.

Marguerite R Irvin, Degui Zhi, Roby Joehanes, Michael Mendelson, Stella Aslibekyan, Steven A Claas, Krista S Thibeault, Nikita Patel, Kenneth Day, Lindsay Waite Jones and 8 more

Open access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
157citing papers in PubMed, 8 pooled it
12.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

157 citing papers in PubMed, 8 syntheses or guidelines pooled it, 225 citations in OpenAlex.

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  6. Guideline
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  9. Trial
  10. DNA methylation of lipid-related genes affects blood lipid levels.Circulation. Cardiovascular genetics · 2015
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97 more citing papers are in PubMed but not listed here.

4 · The record

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5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Marguerite R IrvinFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.). irvinr@uab.edu.
Degui ZhiFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Roby JoehanesFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Michael MendelsonFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Stella AslibekyanFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Steven A ClaasFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Krista S ThibeaultFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Nikita PatelFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Kenneth DayFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Lindsay Waite JonesFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Liming LiangFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Brian H ChenFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Chen YaoFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Hemant K TiwariFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Jose M OrdovasFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Daniel LevyFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Devin AbsherFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Donna K ArnettFrom the Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL (M.R.I., S.A., S.A.C., D.K.A.); Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL (D.Z., H.K.T.); Population Sciences Branch National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Framingham Heart Study, Framingham, MA (R.J., M.M., L.L., B.H.C., C.Y., D.L.); Department of Cardiology, Boston Children's Hospital, Boston, MA (M.M.); Hudson Alpha Institute for Biotechnology, Huntsville, AL (K.S.T, N.P., K.D., L.W.J., D.A.); Departments of Epidemiology and Biostatistics, School of Public Health, Harvard University, Boston, MA (L.L.); and Nutrition and Genomics Laboratory, Jean Mayer-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA (J.M.O.).
Boston Children's Hospital · USUniversity of Alabama at Birmingham · USHudsonAlpha Institute for Biotechnology · USHarvard University · USFramingham Heart Study · US

Funding

Genomewide Association Study of Lipid Response to Fenofibrate and Dietary FatR01HL091357 · NHLBI · UNIVERSITY OF KENTUCKY · PI ARNETT, DONNA K · 2008 to 2018
$5.8M
Epigenetic Determinants of Lipid Response to Dietary Fat and FenofibrateR01HL104135 · NHLBI · UNIVERSITY OF KENTUCKY · PI ARNETT, DONNA K · 2010 to 2015
$5.5M
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS R01 HL091357NHLBI NIH HHS R01 HL104135NHLBI NIH HHS R01 HL104135-01
6 · The paper itself

Abstract

backgroundGenetic research regarding blood lipids has largely focused on DNA sequence variation; few studies have explored epigenetic effects. Genome-wide surveys of DNA methylation may uncover epigenetic factors influencing lipid metabolism. METHODS AND

resultsTo identify whether differential methylation of cytosine-(phosphate)-guanine dinucleotides (CpGs) correlated with lipid phenotypes, we isolated DNA from CD4+ T cells and quantified the proportion of sample methylation at >450 000 CpGs by using the Illumina Infinium HumanMethylation450 Beadchip in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. We modeled the percentage of methylation at individual CpGs as a function of fasting very-low-density lipoprotein cholesterol and triglycerides (TGs) by using mixed linear regression adjusted for age, sex, study site, cell purity, and family structure. Four CpGs (cg00574958, cg17058475, cg01082498, and cg09737197) in intron 1 of carnitine palmitoyltransferase 1A (CPT1A) were strongly associated with very-low low-density lipoprotein cholesterol (P=1.8×10(-21) to 1.6×10(-8)) and TG (P=1.6×10(-26) to 1.5×10(-9)). Array findings were validated by bisulfite sequencing. We performed quantitative polymerase chain reaction experiments demonstrating that methylation of the top CpG (cg00574958) was correlated with CPT1A expression. The association of cg00574958 with TG and CPT1A expression were replicated in the Framingham Heart Study (P=4.1×10(-14) and 3.1×10(-13), respectively). DNA methylation at CPT1A cg00574958 explained 11.6% and 5.5% of the variation in TG in the discovery and replication cohorts, respectively.

conclusionsThis genome-wide epigenomic study identified CPT1A methylation as strongly and robustly associated with fasting very-low low-density lipoprotein cholesterol and TG. Identifying novel epigenetic contributions to lipid traits may inform future efforts to identify new treatment targets and biomarkers of disease risk.

Indexed as

FastingAdultAnticholesteremic AgentsCarnitine O-PalmitoyltransferaseCohort StudiesEpigenomicsFemaleGenome-Wide Association StudyHumansLipoproteins, VLDLMaleMiddle AgedTriglyceridesAnticholesteremic AgentsCarnitine O-PalmitoyltransferaseCPT1A protein, humanLipoproteins, VLDLTriglyceridescholesterolfatty acidsgenetics, medicallipidslipoproteins

Identifiers

PMID24920721
PMCPMC4209699
OpenAlexW2077063343

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