ArticleCirculation. Cardiovascular genetics2014
Rare variant APOC3 R19X is associated with cardio-protective profiles in a diverse population-based survey as part of the Epidemiologic Architecture for Genes Linked to Environment Study.
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18 citing papers in PubMed, 35 citations in OpenAlex.
- Exonic Variation and Its Clinical Impact in 7221 Old Order Amish.American journal of medical genetics. Part A · 2025Article
- Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling.Clinical proteomics · 2024Review
- Exploring apolipoprotein C-III: pathophysiological and pharmacological relevance.Cardiovascular research · 2024Review
- Review
- The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia.International journal of molecular sciences · 2023Review
- APOC-III: a Gatekeeper in Controlling Triglyceride Metabolism.Current atherosclerosis reports · 2023Review
- Genetically Engineered Hamster Models of Dyslipidemia and Atherosclerosis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- ANGPTL3 and Apolipoprotein C-III as Novel Lipid-Lowering Targets.Current atherosclerosis reports · 2021Review
- The GGLEAM Study: Understanding Glaucoma in the Ohio Amish.International journal of environmental research and public health · 2021Article
- Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels.Circulation. Genomic and precision medicine · 2020Article
- The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans.Frontiers in endocrinology · 2020Review
- Emerging Evidence that ApoC-III Inhibitors Provide Novel Options to Reduce the Residual CVD.Current atherosclerosis reports · 2019Review
- Frequency and phenotype consequence of APOC3 rare variants in patients with very low triglyceride levels.BMC medical genomics · 2018Article
- Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine.Journal of lipid research · 2017Article
- Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?Current cardiology reports · 2016Review
- Population Stratification in the Context of Diverse Epidemiologic Surveys Sans Genome-Wide Data.Frontiers in genetics · 2016Article
- Apolipoprotein C-III: a potent modulator of hypertriglyceridemia and cardiovascular disease.Current opinion in endocrinology, diabetes, and obesity · 2015Review
- Cryptic relatedness in epidemiologic collections accessed for genetic association studies: experiences from the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study and the National Health and Nutrition Examination Surveys (NHANES).Frontiers in genetics · 2015Article
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17 authors at 2 institutions in 1 country.
Dana C CrawfordFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.). dana.crawford@case.edu.
Logan DumitrescuFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Robert GoodloeFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Kristin Brown-GentryFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Jonathan BostonFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Bob McClellanFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Cara SutcliffeFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Rachel WisemanFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Paxton BakerFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Margaret A Pericak-VanceFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
William K ScottFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Melissa AllenFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Ping MayoFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Nathalie Schnetz-BoutaudFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Holli H DilksFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Jonathan L HainesFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
Toni I PollinFrom the Institute for Computational Biology (D.C.C., P.M., J.L.H.), Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH (D.C.C., J.L.H.); Center for Human Genetics Research (L.D., R.G., K.B.-G., J.B., B.M., M.A., N.S.-B.), Department of Molecular Physiology and Biophysics (L.D.), Vanderbilt Technologies for Advanced Genomics Core Facility, Vanderbilt University, Nashville, TN (C.S., R.W., P.B., H.H.D.); Hussman Institute for Human Genomics, University of Miami, FL (M.A.P.-V., W.K.S.); and Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (T.I.P.).
University of Miami · USCase Western Reserve University · US
Funding
XENOBIOTIC BIOTRANSFORMATION AND DISPOSITIONP30ES007033 · NIEHS · UNIVERSITY OF WASHINGTON · PI ALI SHOJAIE · 1995 to 2026
$42.5MZonulin Antibodies in Intestinal Permeabilitiy in IDDMM01RR016500 · NCRR · UNIVERSITY OF MARYLAND BALTIMORE · PI OSWALD, LYNN M · 2002 to 2009
$20.2MResearch BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3MGenome-wide Search for CVD Gene-Environment InteractionsU01HL072515 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2002 to 2008
$11.2MGenetic Studies of Dementia in the AmishR01AG019085 · NIA · VANDERBILT UNIVERSITY · PI HAINES, JONATHAN L · 2001 to 2011
$11.0MEpidemiologic Architecture for Genes Linked to Environment (EAGLE)U01HG004798 · NHGRI · VANDERBILT UNIVERSITY · PI CRAWFORD, DANA C · 2008 to 2013
$8.8MLongevity Genes in Founder PopulationsR01AG018728 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2001 to 2005
$3.8MTraining Program on Genetic Variation and Human PhenotypesT32GM080178 · NIGMS · VANDERBILT UNIVERSITY · PI COX, NANCY J, SAMUELS, DAVID C · 2007 to 2021
$3.1MMapping Genes for Mammographic Breast DensityR01CA122844 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DOUGLAS, JULIE A. · 2007 to 2011
$3.0MThe Metabolic Impact of Congenital Heterozygous ApoC-III Deficiency in HumansR01HL104193 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI POLLIN, TONI I. · 2011 to 2015
$3.0MGenetic Studies of Successful Aging in the AmishR01AG019726 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SCOTT, WILLIAM K. · 2003 to 2007
$2.9MGenetic Influences on Coronary Artery CalcificationR01HL088119 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2007 to 2010
$2.8MNCI NIH HHS R01 CA122844NCRR NIH HHS M01 RR016500NCRR NIH HHS M01 RR 16500NHGRI NIH HHS U01 HG004798NHGRI NIH HHS U01HG004798NHLBI NIH HHS N01 HV048195NHLBI NIH HHS N01-HV-48195NHLBI NIH HHS R01 HL088119NHLBI NIH HHS R01 HL104193NHLBI NIH HHS U01 HL072515NHLBI NIH HHS U01 HL084756NHLBI NIH HHS U01 HL72515NIAMS NIH HHS R01 AR046838NIA NIH HHS AG019085NIA NIH HHS AG019726NIA NIH HHS R01 AG018728NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019726NIA NIH HHS R01 AG18728NIDDK NIH HHS P30 DK072488NIEHS NIH HHS 5P30 ES007033-12NIEHS NIH HHS P30 ES007033NIGMS NIH HHS T32 GM080178
Abstract
backgroundA founder mutation was recently discovered and described as conferring favorable lipid profiles and reduced subclinical atherosclerotic disease in a Pennsylvania Amish population. Preliminary data have suggested that this null mutation APOC3 R19X (rs76353203) is rare in the general population. METHODS AND
resultsTo better describe the frequency and lipid profile in the general population, we as part of the Population Architecture using Genomics and Epidemiology I Study and the Epidemiological Architecture for Genes Linked to Environment Study genotyped rs76353203 in 1113 Amish participants from Ohio and Indiana and 19 613 participants from the National Health and Nutrition Examination Surveys (NHANES III, 1999 to 2002, and 2007 to 2008). We found no carriers among the Ohio and Indiana Amish. Of the 19 613 NHANES participants, we identified 31 participants carrying the 19X allele, for an overall allele frequency of 0.08%. Among fasting adults, the 19X allele was associated with lower triglycerides (n=7603; β=-71.20; P=0.007) and higher high-density lipoprotein cholesterol (n=8891; β=15.65; P=0.0002) and, although not significant, lower low-density lipoprotein cholesterol (n=6502; β= -4.85; P=0.68) after adjustment for age, sex, and race/ethnicity. On average, 19X allele participants had approximately half the triglyceride levels (geometric means, 51.3 to 69.7 versus 134.6 to 141.3 mg/dL), >20% higher high-density lipoprotein cholesterol levels (geometric means, 56.8 to 74.4 versus 50.38 to 53.36 mg/dL), and lower low-density lipoprotein cholesterol levels (geometric means, 104.5 to 128.6 versus 116.1 to 125.7 mg/dL) compared with noncarrier participants.
conclusionsThese data demonstrate that APOC3 19X exists in the general US population in multiple racial/ethnic groups and is associated with cardio-protective lipid profiles.
Indexed as
AdultAgedAllelesAmishApolipoprotein C-IIIAtherosclerosisCholesterol, HDLCholesterol, LDLFemaleGene FrequencyGenotypeHaplotypesHumansMaleMiddle AgedNutrition SurveysApolipoprotein C-IIICholesterol, HDLCholesterol, LDLTriglyceridesgenetic association studiesgeneticshigh-density lipoprotein cholesterolmolecular epidemiologytriglycerides
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