Evidence map›Paper›PMID 38538338›Full record

ArticleJournal of atherosclerosis and thrombosis2024

Genetic and Functional Analyses of Patients with Marked Hypo-High-Density Lipoprotein Cholesterolemia.

Yasuhisa Furuta, Yoshinori Osaki, Yoshimi Nakagawa, Song-Iee Han, Masaya Araki, Akito Shikama, Nami Ohuchi, Daichi Yamazaki, Erika Matsuda, Seitaro Nohara and 22 more

Open access · diamondAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of atherosclerosis and thrombosis, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 93% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

32 authors at 11 institutions in 3 countries.

Yasuhisa FurutaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Yoshinori OsakiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Yoshimi NakagawaDivision of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama.
Song-Iee HanLife Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba.
Masaya ArakiDivision of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama.
Akito ShikamaDepartment of Endocrinology and Metabolism, Ibaraki Prefectural Central Hospital, Ibaraki Cancer Center.
Nami OhuchiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Daichi YamazakiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Erika MatsudaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Seitaro NoharaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Yuhei MizunoeLaboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
Kenta KainohDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Yasuhito SueharaDepartment of Hematology, University of Tsukuba Hospital, Tsukuba.
Hiroshi OhnoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Yoshinori TakeuchiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Takafumi MiyamotoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Yuki MurayamaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Yoko SuganoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Hitoshi IwasakiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Ken-Ichi HiranoLaboratory of Novel, Non-invasive, and Nutritional Therapeutics (CNT), Department of Triglyceride Science, Graduate School of Medicine, Osaka University.
Masahiro KosekiDivision of Cardiovascular Medicine, Department of Medicine, Osaka University Graduate School of Medicine.
Shogo NakanoDepartment of Food and Nutritional Sciences, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka.
Hiroaki TokiwaLaboratory of Organic Chemistry, Gifu Pharmaceutical University.
Motohiro SekiyaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Naoya YahagiDivision of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University School of Medicine.
Takashi MatsuzakaDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Kiyotaka NakamagoeDepartment of Neurology, Faculty of Medicine, University of Tsukuba.
Yasushi TomidokoroDepartment of Neurology, Faculty of Medicine, University of Tsukuba.
Jun MitsuiDepartment of Neurology, Graduate School of Medicine, The University of Tokyo.
Shoji TsujiDepartment of Neurology, Graduate School of Medicine, The University of Tokyo.
Hiroaki SuzukiDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Hitoshi ShimanoDepartment of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
University of Tsukuba · JPThe University of Osaka · JPThe University of Tokyo · JPUniversity of Toyama · JPAlliance University · INGifu Pharmaceutical University · JPIbaraki Prefectural Central Hospital · JPJichi Medical University · JPTokyo University of Science · JPUniversity of Shizuoka · JPUniversity of Tsukuba Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimThis study aimed to analyze two cases of marked hypo-high-density lipoprotein (HDL) cholesterolemia to identify mutations in ATP-binding cassette transporter A1 (ABCA1) and elucidate the molecular mechanism by which these novel pathological mutations contribute to hypo-HDL cholesterolemia in Tangier disease.

methodsWild type and mutant expression plasmids containing a FLAG tag inserted at the C-terminus of the human ABCA1 gene were generated and transfected into HEK293T cells. ABCA1 protein expression and cholesterol efflux were evaluated via Western blotting and efflux assay. The difference in the rate of change in protein expression was evaluated when proteolytic and protein-producing systems were inhibited.

resultsIn case 1, a 20-year-old woman presented with a chief complaint of gait disturbance. Her HDL-C level was only 6.2 mg/dL. Tangier disease was suspected because of muscle weakness, decreased nerve conduction velocity, and splenomegaly. Whole-exome analysis showed compound heterozygosity for a W484* nonsense mutation and S1343I missense mutation, which confirmed Tangier disease. Cholesterol efflux decreased by a mixture of W484* and S1343I mutations. The S1343I mutation decreased the protein production rate but increased the degradation rate, decreasing the protein levels. This patient also had Krabbe disease. The endogenous ABCA1 protein level of macrophage cell decreased by knocking down its internal galactocerebrosidase. Case 2, a 51-year-old woman who underwent tonsillectomy presented with peripheral neuropathy, corneal opacity, and HDL-C of 3.4 mg/dL. Whole-exome analysis revealed compound heterozygosity for R579* and R1572* nonsense mutations, which confirmed Tangier disease.

conclusionCase 1 is a new ABCA1 mutation with complex pathogenicity, namely, a W484*/S1343I compound heterozygote with marked hypo-HDL cholesterolemia. Analyses of the compound heterozygous mutations indicated that decreases in ABCA1 protein levels and cholesterol efflux activity caused by the novel S1343I mutation combined with loss of W484* protein activity could lead to marked hypo-HDL cholesterolemia. Galactocerebrosidase dysfunction could also be a potential confounding factor for ABCA1 protein function.

Indexed as

ATP Binding Cassette Transporter 1Cholesterol, HDLFemaleHEK293 CellsHumansMiddle AgedMutationTangier DiseaseYoung AdultABCA1 protein, humanATP Binding Cassette Transporter 1Cholesterol, HDLABCA1Cholesterol effluxHDLTangier disease

Identifiers

PMID38538338
PMCPMC11374561
OpenAlexW4393216123

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
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Registered trials

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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 Socratic graph.