Iron Overload

Iron plays a key role in maintaining the body. It is used in the production of hemoglobin, a protein found in red blood cells, which transports oxygen to muscles and tissues throughout the body. On the other hand, too much iron is detrimental and can cause various significant diseases. C282Y and H63D are mutations found on the HFE gene and are the major cause of inherited iron overload (hereditary hemochromatosis). As a result, iron regulation is disrupted and too much iron is absorbed from a strong transferrin signal as if the body were iron deficient. Consequently, this leads to iron overload, or hemochromatosis. The three most common HFE mutation genotypes in hereditary hemochromatosis are homozygous H63D, homozygous C282Y, and compound H63D/C282Y heterozygous. The most common presence of iron overload is found in hepatocytes found in the liver. To estimate the degree of this disorder, a liver biopsy was performed on approximately two thousand patients in the bariatric surgery program. Of those two thousand patients, 84% had normal liver with no sign of overload and 16% exhibited some form of iron overload, either in hepatocytes, Kupffer cells, or both. DNA was obtained from these patients and Single Nucleotide Polymorphism genotyping assays were designed for the C282Y and H63D HFE mutations in order to determine which alleles are present in these patients and if they are homozygous or heterozygous for these alleles. Patients with or without liver iron overload shared identical levels of HFE mutations, which questions the actual role of the HFE gene in iron overload. By studying the DNA samples of bariatric patients and SNP’s (single nucleotide polymorphisms) through genotyping, this research will support that the presence of both mutations have no difference in serum levels in those with iron found in liver and those without, confirming that the HFE gene is a non-factor in developing iron overload.
Keywords: C282Y mutation, H36D mutation, HFE gene ,