From the Guidelines
The HFE gene plays a crucial role in regulating iron absorption in the body, and its primary purpose is to maintain appropriate iron levels by controlling how much iron is absorbed from food in the intestines. The HFE gene produces a protein that works with other proteins to detect the amount of iron in the body and reduce absorption when iron stores are adequate 1. Mutations in the HFE gene, particularly the C282Y and H63D variants, can lead to hereditary hemochromatosis, a condition characterized by excessive iron absorption and accumulation in tissues and organs 1.
Some key points about the HFE gene and its function include:
- The HFE gene is located on chromosome 6 1
- The gene produces a protein that helps regulate iron absorption 1
- Mutations in the HFE gene, such as C282Y and H63D, can lead to hereditary hemochromatosis 1
- Hereditary hemochromatosis can cause complications such as cirrhosis, heart failure, diabetes, and joint pain if left untreated 1
The importance of the HFE gene in maintaining iron homeostasis cannot be overstated, as iron is essential for many biological processes, including oxygen transport, energy production, and immune function 1. Therefore, the HFE gene's proper functioning is critical to preventing iron overload and the associated complications.
From the Research
HFE Gene Function
- The HFE gene plays a crucial role in regulating iron metabolism in the body 2, 3, 4, 5, 6.
- It influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism 4.
- The HFE gene encodes the MHC class I-like protein HFE that binds beta-2 microglobulin 4.
- Mutations in the HFE gene can lead to hereditary hemochromatosis, an autosomal recessive genetic disease characterized by excessive iron absorption 2, 3, 5, 6.
Iron Homeostasis
- The HFE gene helps regulate iron homeostasis by enabling intestinal crypt cells and reticuloendothelial system to interpret the body's iron requirements and regulate iron absorption and distribution 3.
- The balance between serum transferrin saturation and serum transferrin-receptor concentrations determines the function of HFE in iron metabolism 3.
- HFE mutations can disrupt iron homeostasis, leading to overabsorption of dietary iron and tissue iron deposition 3, 5.
Clinical Significance
- Hereditary hemochromatosis is a common genetic disorder in individuals of European descent, and the HFE gene is responsible for ~90% of hemochromatosis phenotypes in whites of western European descent 4.
- Early detection of HFE gene mutations can help prevent the progression of iron accumulation and the development of clinical symptoms, such as cirrhosis, cardiomyopathy, and diabetes mellitus 2, 6.
- Therapeutic phlebotomy is the primary form of treatment for hereditary hemochromatosis, and genotypic check of the HFE gene is vital for early detection and prevention of the disease 2, 6.