ArticleHepatology (Baltimore, Md.)2018
Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A common variant that alters SUN1 degradation associates with hepatic steatosis and metabolic traits in multiple cohorts.Journal of hepatology · 2023Pooled it
- The inner nuclear membrane protein SUN1 regulates cullin-3 neddylation to maintain insulin signaling.bioRxiv : the preprint server for biology · 2026Article
- Pathogenesis of metabolic dysfunction-associated steatotic liver disease and donor liver damage.iLIVER · 2025Review
- Reduced ZMPSTE24 expression leads to prelamin accumulation and development of steatosis in MASLD patients.Scientific reports · 2025Article
- Enzyme-independent functions of HDAC3 in the adult heart.Acta pharmaceutica Sinica. B · 2025Article
- Hepatocyte-specific loss of LAP2α protects against diet-induced hepatic steatosis, steatohepatitis, and fibrosis in male mice.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Abnormal Cellular Phenotypes Induced by ThreeCells · 2023Article
- Review
- Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk.International journal of molecular sciences · 2021Review
- Sirtuin 1 ameliorates defenestration in hepatic sinusoidal endothelial cells during liver fibrosis via inhibiting stress-induced premature senescence.Cell proliferation · 2021Article
- Review
- Genotype-phenotype analysis of LMNA-related diseases predicts phenotype-selective alterations in lamin phosphorylation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Nuclear envelope-localized torsinA-LAP1 complex regulates hepatic VLDL secretion and steatosis.The Journal of clinical investigation · 2019Article
- Article
- Lamins and Lamin-Associated Proteins in Gastrointestinal Health and Disease.Gastroenterology · 2018Review
- Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins.Nucleus (Austin, Tex.) · 2018Article
- Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial, but twin and familial studies indicate significant heritability, which is not fully explained by currently known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina-associated proteins predispose to NAFLD and used a candidate gene-sequencing approach to test for variants in 10 nuclear lamina-related genes in a cohort of 37 twin and sibling pairs: 21 individuals with and 53 without NAFLD. Twelve heterozygous sequence variants were identified in four lamina-related genes (ZMPSTE24, TMPO, SREBF1, SREBF2). The majority of NAFLD patients (>90%) had at least one variant compared to <40% of controls (P < 0.0001). When only insertions/deletions and changes in conserved residues were considered, the difference between the groups was similarly striking (>80% versus <25%; P < 0.0001). Presence of a lamina variant segregated with NAFLD independently of the PNPLA3 I148M polymorphism. Several variants were found in TMPO, which encodes the lamina-associated polypeptide-2 (LAP2) that has not been associated with liver disease. One of these, a frameshift insertion that generates truncated LAP2, abrogated lamin-LAP2 binding, caused LAP2 mislocalization, altered endogenous lamin distribution, increased lipid droplet accumulation after oleic acid treatment in transfected cells, and led to cytoplasmic association with the ubiquitin-binding protein p62/SQSTM1.
conclusionSeveral variants in nuclear lamina-related genes were identified in a cohort of twins and siblings with NAFLD; one such variant, which results in a truncated LAP2 protein and a dramatic phenotype in cell culture, represents an association of TMPO/LAP2 variants with NAFLD and underscores the potential importance of the nuclear lamina in NAFLD. (Hepatology 2018;67:1710-1725).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.