Genes that modify the hemochromatosis phenotype in mice

Levy, Joanne E.; Montross, Lynne K.; Andrews, Nancy C.

doi:10.1172/jci9635

Cited by 214 publications

(166 citation statements)

References 42 publications

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“…Coinherited mutations in other hemochromatosis genes, such as HAMP and HJV, may have a role, but they are rare. 28,29 In general, the modifier effect of iron genes has been documented in mice, [30][31][32] and these findings have not been fully confirmed in humans. [33][34][35][36][37] Debate continues over the roles of a fatty liver, a high body mass index, 38,39 and polymorphic changes in oxidative stress-related genes, 40 but there is evidence for a strong association between alcohol and the development of hemochromatosis-related cirrhosis.…”

Section: Clinical Aspectsmentioning

confidence: 99%

Hemochromatosis

2007

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This review acknowledges the recent and dramatic advancement in the field of hemochromatosis and highlights the surprising analogies with a prototypic endocrine disease, diabetes. The term hemochromatosis should refer to a unique clinicopathologic subset of ironoverload syndromes that currently includes the disorder related to the C282Y homozygote mutation of the hemochromatosis protein HFE (by far the most common form of hemochromatosis) and the rare disorders more recently attributed to the loss of transferrin receptor 2, HAMP (hepcidin antimicrobial peptide), or hemojuvelin or to certain ferroportin mutations. The defining characteristic of this subset is failure to prevent unneeded iron from entering the circulatory pool as a result of genetic changes compromising the synthesis or activity of hepcidin, the iron hormone. Like diabetes, hemochromatosis results from the complex, nonlinear interaction between genetic and acquired factors. Depending on the underlying mutation, the coinheritance of modifier genes, the presence of nongenetic hepcidin inhibitors, and other host-related factors, the clinical manifestation may vary from simple biochemical abnormalities to severe multiorgan disease. The recognition of the endocrine nature of hemochromatosis suggests intriguing possibilities for new and more effective approaches to diagnosis and treatment. (HEPATOLOGY 2007;46:1291-1301

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Section: Clinical Aspectsmentioning

confidence: 99%

Hemochromatosis

2007

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“…Simply using the genotype is problematic as the expression ('penetrance') of the gene varies widely. There appear to be modifier genes which modulate the expression of HFE mutations 17,18 which, when coupled with the individual variations of iron loss (such as in menstruating women), result in considerable variation in the clinical expression of at risk (C282Y/C282Y and C282Y/H63D) genotypes.…”

Section: Hfe Mutations and Gene Penetrancementioning

confidence: 99%

Iron overload syndromes and the liver

Batts

2007

Modern Pathology

135

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Section: Introductionmentioning

confidence: 99%

“…The regulatory mechanism for iron homeostasis is still uncertain, but several proteins, and thus several genes, have been identified as contributors to the process [5]. Genetic variants in the iron regulatory systems influence the likelihood of iron deficiency, as is seen in mouse models [5]. The transferrin G277S variant of the transferrin gene has been found primarily in people of European ancestry [7], with a frequency of 0.0634 (111 of 1752 alleles) and according to Lee et al [6], the G277S mutation is the only mutation found to influence iron metabolism and predispose menstruating white women to iron deficiency anaemia.…”

Section: Introductionmentioning

confidence: 99%