Evidence map›Paper›PMID 25127531›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Aberrant hetero-disulfide bond formation by the hypertriglyceridemia-associated p.Gly185Cys APOA5 variant (rs2075291).

Vineeta Sharma, Andrzej Witkowski, H Ewa Witkowska, Andrew Dykstra, Jens B Simonsen, Lisa Nelbach, Jennifer A Beckstead, Clive R Pullinger, John P Kane, Mary J Malloy and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  2. Article
  3. Article
  4. Chylomicronemia through a burr hole: A case report.Frontiers in cardiovascular medicine · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Vineeta SharmaFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Andrzej WitkowskiFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
H Ewa WitkowskaFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Andrew DykstraFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Jens B SimonsenFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Lisa NelbachFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Jennifer A BecksteadFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Clive R PullingerFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
John P KaneFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Mary J MalloyFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Gordon WatsonFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Trudy M ForteFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.).
Robert O RyanFrom the Children's Hospital Oakland Research Institute, CA (V.S., A.W., J.B.S., L.N., J.A.B., G.W., T.M.F., R.O.R.); Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Sandler-Moore Mass Spectrometry Core Facility, San Francisco, CA (H.E.W., A.D.); and Cardiovascular Research Institute, University of California, San Francisco (C.R.P., J.P.K., M.J.M.). rryan@chori.org.
Cardiovascular Institute of the South · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
Effect of Apolipoprotein Structural AdaptabilityR37HL064159 · NHLBI · UNIVERSITY OF NEVADA RENO · PI RYAN, ROBERT O'MARA · 2010 to 2019
$4.1M
EFFECT OF APOLIPOPROTEIN STRUCTURAL ADAPTABILITYR01HL064159 · NHLBI · CHILDREN'S HOSPITAL &RES CTR AT OAKLAND · PI RYAN, ROBERT O'MARA · 2000 to 2009
$3.6M
NCI NIH HHS P30 CA082103NHLBI NIH HHS HL-64159NHLBI NIH HHS R01 HL064159NHLBI NIH HHS R37 HL064159
6 · The paper itself

Abstract

objectiveApolipoprotein A-V (apoA-V) is a low-abundance plasma protein that modulates triacylglycerol homeostasis. Gene transfer studies were undertaken in apoa5 (-/-) mice to define the mechanism underlying the correlation between the single-nucleotide polymorphism c.553G>T in APOA5 and hypertriglyceridemia. APPROACH AND

resultsAdeno-associated virus (AAV) 2/8-mediated gene transfer of wild-type apoA-V induced a dramatic lowering of plasma triacylglycerol in apoa5 (-/-) mice, whereas AAV2/8-Gly162Cys apoA-V (corresponding to the c.553G>T single-nucleotide polymorphism: rs2075291; p.Gly185Cys when numbering includes signal sequence) had a modest effect. Characterization studies revealed that plasma levels of wild-type and G162C apoA-V in transduced mice were similar and within the physiological range. Fractionation of plasma from mice transduced with AAV2/8-G162C apoA-V indicated that, unlike wild-type apoA-V, >50% of G162C apoA-V was recovered in the lipoprotein-free fraction. Nonreducing SDS-PAGE immunoblot analysis provided evidence that G162C apoA-V present in the lipoprotein-free fraction, but not that portion associated with lipoproteins, displayed altered electrophoretic mobility consistent with disulfide-linked heterodimer formation. Immunoprecipitation followed by liquid chromatography/mass spectrometry of human plasma from subjects homozygous for wild-type APOA5 and c.553G>T APOA5 revealed that G162C apoA-V forms adducts with extraneous plasma proteins including fibronectin, kininogen-1, and others.

conclusionsSubstitution of Cys for Gly at position 162 of mature apoA-V introduces a free cysteine that forms disulfide bonds with plasma proteins such that its lipoprotein-binding and triacylglycerol-modulation functions are compromised.

Indexed as

AnimalsApolipoprotein A-VApolipoproteinsApolipoproteins ABiomarkersCase-Control StudiesDependovirusDisease Models, AnimalDisulfidesGenetic VectorsGene Transfer TechniquesHEK293 CellsHumansHypertriglyceridemiaMaleMiceAPOA5 protein, humanApoa5 protein, mouseApolipoprotein A-VApolipoproteinsApolipoproteins ABiomarkersDisulfidesTriglyceridesgenetic therapylipoproteinspolymorphism, single nucleotidetriglycerides

Identifiers

PMID25127531
PMCPMC4178935
OpenAlexW2135413482

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.