ArticleCirculation. Cardiovascular genetics2014
The WWOX gene modulates high-density lipoprotein and lipid metabolism.
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Article in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36citing papers in PubMed
1.2field-weighted citation impact, top 24% of its field
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Who cites it
36 citing papers in PubMed, 44 citations in OpenAlex.
- Developmental programming: Differing impact of prenatal testosterone and prenatal bisphenol-A -treatment on hepatic methylome in female sheep.Molecular and cellular endocrinology · 2025Article
- Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge.Functional & integrative genomics · 2025Review
- Genome-wide identification and functional validation of the WW domain containing oxidoreductase gene associated with sleep duration.Scientific reports · 2025Article
- WWOX tuning of oleic acid signaling orchestrates immunosuppressive macrophage polarization and sensitizes hepatocellular carcinoma to immunotherapy.Journal for immunotherapy of cancer · 2024Article
- Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.International journal of molecular sciences · 2023Article
- WWOX P47T partial loss-of-function mutation induces epilepsy, progressive neuroinflammation, and cerebellar degeneration in mice phenocopying human SCAR12.Progress in neurobiology · 2023Article
- WWOX and metabolic regulation in normal and pathological conditions.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Identification of recurrent variants implicated in disease in bicuspid aortic valve patients through whole-exome sequencing.Human genomics · 2022Article
- Article
- TheInternational journal of molecular sciences · 2022Article
- Article
- Neonatal neuronal WWOX gene therapy rescues Wwox null phenotypes.EMBO molecular medicine · 2021Article
- Review
- Molecular Biology of theCells · 2021Review
- Cellular Expression and Subcellular Localization of Wwox Protein During Testicular Development and Spermatogenesis in Rats.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Article
- Associations betweenAging · 2021Article
- WWOX Loss of Function in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2020Review
- Roles of Farnesyl-Diphosphate Farnesyltransferase 1 in Tumour and Tumour Microenvironments.Cells · 2020Review
- Wwox deficiency leads to neurodevelopmental and degenerative neuropathies and glycogen synthase kinase 3β-mediated epileptic seizure activity in mice.Acta neuropathologica communications · 2020Article
- Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development.Frontiers in neuroscience · 2020Article
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Authors and funding
18 authors at 3 institutions in 1 country.
Iulia IatanFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Hong Y ChoiFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Isabelle RuelFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
M V Prasad Linga ReddyFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Hyunsuk KilFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Jaeho LeeFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Mohammad Abu OdehFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Zaidoun SalahFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Muhannad Abu-RemailehFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Daphna Weissglas-VolkovFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Elina NikkolaFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Mete CivelekFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Zuhier AwanFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Carlo M CroceFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Rami I AqeilanFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Päivi PajukantaFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
C Marcelo AldazFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.).
Jacques GenestFrom the Cardiovascular Research Laboratories, Department of Biochemistry, Faculty of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada (I.I., H.Y.C., I.R., Z.A., J.G.); Department of Human Genetics (M.V.P.L.R., D.W.-V., E.N., P.P.) and Department of Medicine (M.V.P.L.R., D.W.-V., E.N., P.P.), David Geffen School of Medicine at University of California at Los Angeles; Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville (H.K., J.L., C.M.A.); The Lautenberg Cancer Research Center, Department of Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel (M.A.O., M.A.-R., R.I.A.); The Lautenberg Center for Immunology and Cancer Research, Department of Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel and Al-Quds-Bard College for Arts and Sciences, Al-Quds University, East Jerusalem-Abu Dis, Palestine (Z.S.); and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus (M.C., C.M.C., R.I.A.). jacques.genest@mcgill.ca.
University of California, Los Angeles · USCancer Research Center · USThe University of Texas MD Anderson Cancer Center · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MSystems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 1985 to 2019
$50.2MTraining Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6MGenomics of dyslipidemia in MexicansR01HL095056 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJUKANTA, PAIVI · 2009 to 2018
$5.9MCharacterization of WWOX, the Cancer Gene Spanning FREA16DR01CA102444 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ALDAZ, C. MARCELO · 2003 to 2014
$3.3MCIHR MOP 15042CIHR MOP 97752NCI NIH HHS R01 CA102444NCI NIH HHS R01 CA102444-7NHGRI NIH HHS T32 HG002536NHLBI NIH HHS HL095056NHLBI NIH HHS HL-28481NHLBI NIH HHS P01 HL028481NHLBI NIH HHS R01 HL095056
Abstract
backgroundLow levels of high-density lipoprotein (HDL) cholesterol constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase (WWOX) gene and HDL cholesterol levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOX in HDL and lipid metabolism. METHODS AND
resultsUsing next-generation resequencing of the WWOX region, we first identified 8 variants significantly associated and perfectly segregating with the low-HDL trait in 2 multigenerational French Canadian dyslipidemic families. To understand in vivo functions of WWOX, we used liver-specific Wwox(hep-/-) and total Wwox(-/-) mice models, where we found decreased ApoA-I and Abca1 levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox(-/-), but not Wwox(hep-/-) littermates, also showed marked reductions in serum HDL cholesterol concentrations, concordant with the low-HDL findings observed in families. We next obtained evidence of a sex-specific effect in female Wwox(hep-/-) mice, where microarray analyses revealed an increase in plasma triglycerides and altered lipid metabolic pathways. We further identified a significant reduction in ApoA-I and Lpl and an upregulation in Fas, Angptl4, and Lipg, suggesting that the effects of Wwox involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1 pathway, and fatty acid biosynthesis/triglyceride metabolism.
conclusionsOur data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants. These findings thus describe a novel gene involved in cellular lipid homeostasis, which effects may impact atherosclerotic disease development.
Indexed as
AdolescentAdultAgedAllelesAngiopoietin-Like Protein 4AngiopoietinsAnimalsApolipoprotein A-IATP Binding Cassette Transporter 1Cholesterol, HDLChromosomes, Human, Pair 16fas ReceptorFemaleHaplotypesHigh-Throughput Nucleotide SequencingHumansAngiopoietin-Like Protein 4AngiopoietinsAngptl4 protein, mouseApolipoprotein A-IATP Binding Cassette Transporter 1Cholesterol, HDLFas protein, mousefas ReceptorLipaseLipg protein, mouseLipoproteins, HDLOxidoreductasesTriglyceridesTumor Suppressor ProteinsWW Domain-Containing OxidoreductaseWWOX protein, humanWwox protein, mouseABCA1Apolopoprotein A-Icardiovascular diseasesgeneticsHDL cholesterollipidsWWOX protein
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