ArticleBiology of sex differences2022
Chromosomal and gonadal sex drive sex differences in lipids and hepatic gene expression in response to hypercholesterolemia and statin treatment.
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.
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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.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026Article
- Reappraisal of the MASLD predictive factors: insights beyond the surface.Journal of gastroenterology · 2026Article
- Association of Statin Use with Reduced Primary Liver Cancer Risk, Independent of Age and Cirrhosis Protection in MASLD.Cancers · 2026Article
- Age-specific protective effects of statins against cirrhosis in patients with chronic liver enzyme elevation associated with metabolic dysfunction: a retrospective cohort study of electronic health records.EClinicalMedicine · 2025Article
- Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences.Acta neuropathologica communications · 2025Article
- Lipoprotein Metabolism, Dyslipidemia, and Lipid-Lowering Therapy in Women: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2024Review
- X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction.Nature communications · 2024Article
- Responses to Many Anti-Aging Interventions Are Sexually Dimorphic.The world journal of men's health · 2024Review
- Review
- The impact of chromosomal sex on cardiometabolic health and disease.Trends in endocrinology and metabolism: TEM · 2023Review
- Review
- The frequency of majorPharmacogenomics · 2023Article
- The role of gonadal hormones and sex chromosomes in sex-dependent effects of early nutrition on metabolic health.Frontiers in endocrinology · 2023Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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.
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