1. The Penetrance of Hemochromatosis: Mice to the Rescue
Antonello Pietrangelo 
Gastroenterology 
Volume 132, Issue 2, Pages (February 2007)
DOI: /j.gastro
Copyright © 2007 AGA Institute Terms and Conditions

2. Figure 1
Known and postulated modifiers of human HFE-related hemochromatosis. Most C282Y homozygotes experience a progressive expansion of the plasma iron compartment reflected by increasing saturation of the plasma iron transporter, transferrin. Its progression can be accelerated by high dietary iron intake or attenuated by active iron utilization and/or loss. In some cases, disease expression never goes beyond this “biochemical phase,” but in over half of all C282Y homozygotes, the plasma iron overload is followed by progressive accumulation of iron in parenchymal tissues of the liver and other organs, heralded by rising serum levels of the iron-storage protein, ferritin. The third phase, which occurs in a limited percentage of cases, is manifested by markedly elevated levels of serum ferritin, along with signs and symptoms of target organ impairment. Susceptibility to organ disease may depend on modifier genes that affect the rate of iron accumulation in the bloodstream and tissues and/or the propensity to oxidant damage, tissue repair, and fibrogenesis. Among various factors that had been postulated as putative hemochromatosis modifiers,3 some are now either known (red) or suspected (pink) to aggravate the hemochromatosis phenotype based on human studies, whereas others act as modifiers of the iron loading phenotype in mice hemochromatosis (blue; modified from Pietrangelo,3 with permission).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions