ArticleHepatology (Baltimore, Md.)2015
Exome sequencing in HFE C282Y homozygous men with extreme phenotypes identifies a GNPAT variant associated with severe iron overload.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review.World journal of gastroenterology · 2016Pooled it
- Isolated Non-Progressive Hemidystonia in a Patient Homozygous for H63D Variant of Hereditary Hemochromatosis: A Case Report and Systematic Literature Review of Movement Disorders in Hereditary Hemochromatosis.Diagnostics (Basel, Switzerland) · 2025Article
- Serum Ferritin in Women WithEJHaem · 2025Article
- The ancestral haplotype markers HLA -A3 and B7 do not influence the likelihood of advanced hepatic fibrosis or cirrhosis in HFE hemochromatosis.Scientific reports · 2023Article
- An exome-wide study of renal operational tolerance.Frontiers in medicine · 2022Article
- Revisiting hemochromatosis: geneticAnnals of translational medicine · 2021Review
- Article
- Increased frequency of GNPAT p.D519G in compound HFE p.C282Y/p.H63D heterozygotes with elevated serum ferritin levels.Blood cells, molecules & diseases · 2020Article
- Dysregulated hepcidin response to dietary iron in male mice with reduced Gnpat expression.Bioscience reports · 2020Article
- Gnpat does not play an essential role in systemic iron homeostasis in murine model.Journal of cellular and molecular medicine · 2020Article
- Inherited iron overload disorders.Translational gastroenterology and hepatology · 2020Review
- Identification of genetic variants associated with tacrolimus metabolism in kidney transplant recipients by extreme phenotype sampling and next generation sequencing.The pharmacogenomics journal · 2019Observational
- Exonic sequencing identifies TLR1 genetic variation associated with mortality in Thais with melioidosis.Emerging microbes & infections · 2019Article
- Iron as a Therapeutic Target inPharmaceuticals (Basel, Switzerland) · 2018Review
- Cirrhosis in Hemochromatosis: Independent Risk Factors in 368 HFE p.C282Y Homozygotes.Annals of hepatology · 2018Article
- Haemochromatosis.Nature reviews. Disease primers · 2018Review
- Hemochromatosis: a model of metal-related human toxicosis.Environmental science and pollution research international · 2018Article
- Inherited Disorders of Iron Overload.Frontiers in nutrition · 2018Review
- HFE hemochromatosis screening in patients with severe hip osteoarthritis: A prospective cross-sectional study.PloS one · 2018Article
- Concepts of Genomics in Kidney Transplantation.Current transplantation reports · 2017Article
Corrections and comments
Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
Abstract
unlabelledTo identify polymorphisms associated with variability of iron overload severity in HFE-associated hemochromatosis, we performed exome sequencing of DNA from 35 male HFE C282Y homozygotes with either markedly increased iron stores (n = 22; cases) or with normal or mildly increased iron stores (n = 13; controls). The 35 participants, residents of the United States, Canada, and Australia, reported no or light alcohol consumption. Sequencing data included 82,068 single-nucleotide variants, and 10,337 genes were tested for a difference between cases and controls. A variant in the GNPAT gene showed the most significant association with severe iron overload (P = 3 × 10(-6) ; P = 0.033 by the likelihood ratio test after correction for multiple comparisons). Sixteen of twenty-two participants with severe iron overload had glyceronephosphate O-acyltransferase (GNPAT) polymorphism p.D519G (rs11558492; 15 heterozygotes, one homozygote). No control participant had this polymorphism. To examine functional consequences of GNPAT deficiency, we performed small interfering RNA-based knockdown of GNPAT in the human liver-derived cell line, HepG2/C3A. This knockdown resulted in a >17-fold decrease in expression of the messenger RNA encoding the iron-regulatory hormone, hepcidin.
conclusionGNPAT p.D519G is associated with a high-iron phenotype in HFE C282Y homozygotes and may participate in hepcidin regulation.
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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.