How does genetic variation increase the risk of iron deficiency?

Iron is a mineral with several essential functions in the body. It constitutes the core of both hemoglobin, the molecule that carries oxygen from the lungs to the rest of the body, and myoglobin, a protein that provides oxygen to the muscles. Iron is also essential for growth, normal cell function, and the production of connective tissue and some hormones.

Iron in our food comes in two forms: heme and non-heme. Plant-based and fortified foods such as cereals only contain non-heme iron. Animal sources contain both types. Non-heme iron has lower rates of absorption and use in the body (bioavailability) than heme iron. 

Iron metabolism requires the cooperation of many genes. Genetic variants of two genes, TF and TMPRSS6, are linked to lower iron levels in the blood. The TF gene encodes an iron-binding protein called transferrin. Transferrin controls how much free iron is found in the blood. Individuals who inherit the TF variant make more transferrin, but this altered protein binds less iron, so less iron is transported around the body.  Variants of the TMPRSS6 gene (which encodes matriptase-2) affect the control of a second protein called hepcidin. Hepcidin decreases both the absorption of iron in the intestines and the release of iron from blood and liver stores, resulting in lower blood iron levels. Individuals with TMPRSS6 variants make less matriptase-2. This means hepcidin levels remain abnormally high, preventing the absorption of more iron from the diet. 

Low iron levels inhibit the production of hemoglobin, resulting in a reduced red blood cell count. When the body can’t supply enough red blood cells to meet its demands, it manifests as anemia, which affects over 1.6 billion people around the globe. Symptoms include tiredness, fatigue, pale skin, shortness of breath, headaches, dizziness, and unusual cravings for non-nutritive substances such as ice or dirt. These initial symptoms of deficiency can go unnoticed, but if left untreated, anemia can have serious repercussions, including impaired cognitive function, disturbances in the digestive system, and impaired immunity. Pregnant women, young children and frequent blood donors are at a much higher risk of iron deficiency.