ArticleHuman molecular genetics2015
Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses 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
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT.Communications biology · 2022Pooled it
- A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.Communications biology · 2021Pooled it
- Article
- Iron and Liver Disease.Advances in experimental medicine and biology · 2025Review
- [A case report of mild hereditary hemochromatosis caused by HAMP gene mutation].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Lung microhaemorrhage drives oxidative/inflammatory damage in αERJ open research · 2023Article
- Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses.International journal of molecular sciences · 2023Article
- Identification of iron metabolism-related genes in the circulation and myocardium of patients with sepsisFrontiers in cardiovascular medicine · 2023Article
- Article
- TAM-ing the CIA-Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia.Frontiers in oncology · 2021Article
- Intrahepatic heteropolymerization of M and Z alpha-1-antitrypsin.JCI insight · 2020Article
- Inherited iron overload disorders.Translational gastroenterology and hepatology · 2020Review
- Article
- Heterozygosity for the alpha-1-antitrypsin Z allele in cirrhosis is associated with more advanced disease.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2018Article
- Iron in the Tumor Microenvironment-Connecting the Dots.Frontiers in oncology · 2018Review
- Iron deficiency or anemia of inflammation? : Differential diagnosis and mechanisms of anemia of inflammation.Wiener medizinische Wochenschrift (1946) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Liver disease due to alpha-1-antitrypsin deficiency (A1ATD) is associated with hepatic iron overload in a subgroup of patients. The underlying cause for this association is unknown. The aim of the present study was to define the genetics of this correlation and the effect of alpha-1-antitrypsin (A1AT) on the expression of the iron hormone hepcidin. Full exome and candidate gene sequencing were carried out in a family with A1ATD and hepatic iron overload. Regulation of hepcidin expression by A1AT was studied in primary murine hepatocytes. Cells co-transfected with hemojuvelin (HJV) and matriptase-2 (MT-2) were used as a model to investigate the molecular mechanism of this regulation. Observed familial clustering of hepatic iron overload with A1ATD suggests a genetic cause, but genotypes known to be associated with hemochromatosis were absent. Individuals homozygous for the A1AT Z-allele with environmental or genetic risk factors such as steatosis or heterozygosity for the HAMP non-sense mutation p.Arg59* presented with severe hepatic siderosis. In hepatocytes, A1AT induced hepcidin mRNA expression in a dose-dependent manner. Experiments in overexpressing cells show that A1AT reduces cleavage of the hepcidin inducing bone morphogenetic protein co-receptor HJV via inhibition of the membrane-bound serine protease MT-2. The acute-phase protein A1AT is an inducer of hepcidin expression. Through this mechanism, A1ATD could be a trigger of hepatic iron overload in genetically predisposed individuals or patients with environmental risk factors for hepatic siderosis.
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.