Evidence map›Paper›PMID 36333813›Full record

ArticleBiology of sex differences2022

Chromosomal and gonadal sex drive sex differences in lipids and hepatic gene expression in response to hypercholesterolemia and statin treatment.

Carrie B Wiese, Zoey W Agle, Peixiang Zhang, Karen Reue

Open access · goldFull text read
In one paragraph

Article in Biology of sex differences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026
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  6. Review
  7. Article
  8. Review
  9. Review
  10. The impact of chromosomal sex on cardiometabolic health and disease.Trends in endocrinology and metabolism: TEM · 2023
    Review
  11. Review
  12. The frequency of majorPharmacogenomics · 2023
    Article
  13. Review
  14. Global & regional health technology assessment
    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

4 authors at 1 institution in 1 country.

Carrie B WieseDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Zoey W AgleDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Peixiang ZhangDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Karen ReueDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA. reuek@ucla.edu.ORCID 0000-0002-7487-2624
University of California, Los Angeles · US

Funding

Pharmacogenomics of Statin TherapyP50GM115318 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRAUSS, RONALD M, LUSIS, ALDONS JAKE · 2015 to 2019
$14.0M
Sex Differences in the Metabolic SyndromeU54DK120342 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2018 to 2022
$7.6M
A novel gene and mechanisms for statin-induced myopathy in the mouseR21AR077782 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN, ZHANG, PEIXIANG · 2020 to 2021
$372k
Epigenetic mechanisms underlying sex differences in obesityF32DK134148 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WIESE, CARRIE BETH · 2023 to 2024
$121k
NIAMS NIH HHS R21 AR077782NIDDK NIH HHS F32 DK134148NIDDK NIH HHS U54 DK120342NIGMS NIH HHS P50 GM115318
6 · The paper itself

Abstract

backgroundBiological sex impacts susceptibility and presentation of cardiovascular disease, which remains the leading cause of death for both sexes. To reduce cardiovascular disease risk, statin drugs are commonly prescribed to reduce circulating cholesterol levels through inhibition of cholesterol synthesis. The effectiveness of statin therapy differs between individuals with a sex bias in the frequency of adverse effects. Limited information is available regarding the mechanisms driving sex-specific responses to hypercholesterolemia or statin treatment.

methodsFour Core Genotypes mice (XX and XY mice with ovaries and XX and XY mice with testes) on a hypercholesteremic Apoe

resultsIn a hypercholesterolemic state, gonadal sex influenced the expression levels of more than 3000 genes, and chromosomal sex impacted expression of nearly 1400 genes, which were distributed across all autosomes as well as the sex chromosomes. Gonadal sex uniquely influenced the expression of ER stress response genes, whereas chromosomal and gonadal sex influenced fatty acid metabolism gene expression in hypercholesterolemic mice. Sex-specific effects on gene regulation in response to statin treatment included a compensatory upregulation of cholesterol biosynthetic gene expression in mice with XY chromosome complement, regardless of presence of ovaries or testes.

conclusionGonadal and chromosomal sex have independent effects on the hepatic transcriptome to influence different cellular pathways in a hypercholesterolemic environment. Furthermore, chromosomal sex in particular impacted the cellular response to statin treatment. An improved understanding of how gonadal and chromosomal sex influence cellular response to disease conditions and in response to drug treatment is critical to optimize disease management for all individuals.

Indexed as

Cardiovascular DiseasesHydroxymethylglutaryl-CoA Reductase InhibitorsHypercholesterolemiaAnimalsFemaleGene ExpressionLipidsMaleMiceSex CharacteristicsX ChromosomeHydroxymethylglutaryl-CoA Reductase InhibitorsLipids

Identifiers

PMID36333813
PMCPMC9636767
OpenAlexW4308273171

What Socratic holds

Textfull text, public
LicenceCC BY
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 Socratic graph.