Mutation Analysis and Allele Frequencies of HFE Gene C282Y, H63D and S65D in Patients with Hyperferritinemia and Healthy Controls from a City in Northeastern Brazil

Hereditary hemochromatosis (HH) is a genetic disease caused by high iron absorption and deposition in several organs. This accumulation results in clinical disturbances such as cirrhosis, arthritis, cardiopathies, diabetes, sexual disorders and skin darkening. The C282Y mutation is well defined in hemochromatosis etiology. Two other mutations have been described, H63D and S65C, associated with a milder form of the disease. The aims of this study were to identify the H63D, S65C and C282Y genetic mutations in the hemochromatosis gene and assess the frequency of these mutations in the HFE protein gene in patients with hyperferritinemia which are sent to the DNA Center laboratory in Natal, Rio Grande do Norte state, in addition to evaluating the correlation between the H63D, C282Y and S65C mutations in hereditary hemochromatosis and serum ferritin. The biochemical dosages and molecular analyses are carried out using the enzymatic method and PCR with enzymatic restriction, respectively. Of the 300 patients investigated, 48.7% showed no mutation and 51.3% some type of mutation: 4.4 % exhibited C282Y heterozygous mutation; 2.7% C282Y homozygous mutation; 31.9% H63D heterozygous mutation; 8.1% H63D homozygous mutation; and 5.1%, heterozygous mutation in both genes. The S65C mutation was studied in 112 patients, 2.7% with heterozygous mutation (S65D/WT) and 1.8% with double heterozygosity (H63D/S65C). With regard to sex, we observed the highest number of cases with molecular changes in men compared to women in the two mutations evaluated. Since it is considered a public health problem and exhibits low toxicity with treatment, early genetic diagnosis of HH is recommended, especially in patients with elevated serum ferritin, thereby preventing severe clinical manifestations resulting from late diagnosis. Our findings show the importance of genetic studies in patients with suspected hereditary hemochromatosis due to the high incidence of this hereditary disease in our region.