Evidence map›Paper›PMID 39537501›Full record

ArticleJournal of clinical lipidology

Identification and functional analysis of novel homozygous LMF1 variants in severe hypertriglyceridemia.

Candy Bedoya, Rishi Thomas, Anna Bjarvin, Wilbur Ji, Hanien Samara, Jody Tai, Laurie Green, Philip H Frost, Mary J Malloy, Clive R Pullinger and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical lipidology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

12 authors.

Candy BedoyaDepartment of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA (Dr Bedoya, Thomas, Bjarvin, Ji, Samara, Tai, and Péterfy).
Rishi ThomasDepartment of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA (Dr Bedoya, Thomas, Bjarvin, Ji, Samara, Tai, and Péterfy).
Anna BjarvinDepartment of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA (Dr Bedoya, Thomas, Bjarvin, Ji, Samara, Tai, and Péterfy).
Wilbur JiDepartment of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA (Dr Bedoya, Thomas, Bjarvin, Ji, Samara, Tai, and Péterfy).
Hanien SamaraDepartment of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA (Dr Bedoya, Thomas, Bjarvin, Ji, Samara, Tai, and Péterfy).
Jody TaiDepartment of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA (Dr Bedoya, Thomas, Bjarvin, Ji, Samara, Tai, and Péterfy).
Laurie GreenCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA (Drs Green, Malloy, Pullinger, and Kane).
Philip H FrostCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA (Drs Green, Malloy, Pullinger, and Kane).
Mary J MalloyCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA (Drs Green, Malloy, Pullinger, and Kane).
Clive R PullingerCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA (Drs Green, Malloy, Pullinger, and Kane).
John P KaneCardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA (Drs Green, Malloy, Pullinger, and Kane).
Miklós PéterfyDepartment of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA (Dr Bedoya, Thomas, Bjarvin, Ji, Samara, Tai, and Péterfy). Electronic address: mpeterfy@westernu.edu.

Funding

Molecular Mechanisms of Lipase Maturation and SecretionR01HL127155 · NHLBI · WESTERN UNIVERSITY OF HEALTH SCIENCES · PI PETERFY, MIKLOS · 2015 to 2018
$1.6M
Lipase Maturation Factor 1 in HypertriglyceridemiaR15HL154071 · NHLBI · WESTERN UNIVERSITY OF HEALTH SCIENCES · PI PETERFY, MIKLOS · 2021 to 2021
$423k
NHLBI NIH HHS R01 HL127155NHLBI NIH HHS R15 HL154071
6 · The paper itself

Abstract

backgroundThe genetic basis of hypertriglyceridemia (HTG) is complex and includes variants in lipase maturation factor 1 (LMF1), an endoplasmic reticulum (ER)-chaperone involved in the post-translational activation of lipoprotein lipase (LPL).

objectiveThe objective of this study was to identify and functionally characterize biallelic LMF1 variants in patients with HTG.

methodsGenomic DNA sequencing was used to identify biallelic LMF1 variants in HTG patients without deleterious variants in LPL, apolipoprotein C-II (APOC2), glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) or apolipoprotein A-V (APOA5). LMF1 variants were functionally evaluated by in silico analyses and assessing their impact on LPL activity, LMF1 protein expression, and specific activity in transiently transfected HEK293 cells.

resultsWe identified four homozygous LMF1 variants in patients with severe HTG: two novel rare variants (p.Asn147Lys and p.Pro246Arg) and two low-frequency variants (p.Arg354Trp and p.Arg364Gln) previously reported at heterozygosity. We demonstrate that all four variants reduce the secretion of enzymatically active LPL by impairing the specific activity of LMF1, whereas p.Asn147Lys also diminishes LMF1 protein expression.

conclusionThis study extends the role of LMF1 as a genetic determinant in severe HTG and demonstrates that rare and low-frequency LMF1 variants can underlie this condition through distinct molecular mechanisms. The clinical phenotype of patients affected by partial loss of LMF1 function is consistent with multifactorial chylomicronemia syndrome (MCS) and suggests that secondary factors and additional genetic determinants contribute to HTG in these subjects.

Indexed as

HomozygoteHypertriglyceridemiaMembrane ProteinsAdultFemaleHEK293 CellsHumansLipoprotein LipaseMaleMiddle AgedLipoprotein LipaseLMF1 protein, humanMembrane ProteinsFamilial chylomicronemia syndromeHypertriglyceridemiaLipase maturation factor 1Multifactorial chylomicronemia syndrome

Identifiers

PMID39537501
PMCPMC12534165

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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 OpenQuestion graph.