B-211 Prevalence of C282Y, H63D and S65C Mutations in the HFE Gene among Brazilian Individuals. Data from a Clinical Laboratory

Background Hereditary hemochromatosis (HH) is an autosomal recessive disorder caused by mutations in the HFE gene and is characterized by the risk of iron overload and deposition in organs, including the liver, pancreas, and heart. The homozygous C282Y genotype of the HFE gene is strongly associated with the disease, with more than 80% of cases presenting clinically evident hemochromatosis. The aim of this study was to determine the prevalence of the C282Y, H63D, and S65C mutations in the HFE gene among individuals tested in a clinical laboratory and to correlate these mutations with transferrin saturation (TS) and ferritin levels for each genotype. Methods This is a retrospective study based on individuals tested for the detection of C282Y, H63D, and S65C mutations in the HFE gene using molecular diagnostics through real-time PCR with TaqMan probes in a clinical laboratory in São Paulo between January 2020 and December 2024. DNA extraction was performed using a commercial kit, following the manufacturer*s recommendations. The results were stratified by gender, age, and genotypic frequency. Statistical analysis was conducted using nonparametric ANOVA and the post-Durbin-Conover test with Jamovi V 2.3.24 software. Results Among the 787 individuals studied, 45.5% (358) had some type of mutation in the HFE gene, of which 45.5% (163/358) were between 41 and 60 years old, and 76% (272/358) were male. The most frequently altered genotypes were heterozygosity for H63D and C282Y, at 55.9% and 14.5%, respectively. However, other genotypes were observed less frequently, such as H63D/H63D (9.8%), C282Y/H63D (8.1%), C282Y/C282Y (7.5%), and S65C/WT (3.1%), genotypic profiles H63D/S65C (0,8%) and C282Y/S65C (0.3%) differing from those typically reported, were observed in 3 and 1 individuals, respectively. Of the 358 individuals, 54 had both TS and ferritin data available within a period of up to 2 months before or after the genetic test. Based on these data, individuals homozygous for the C282Y mutation had an average TS of 81.5% (57.2–94.9%) and ferritin of 867 ng/mL (192–2051.6 ng/mL), higher averages compared to those with other genotypes. Individuals with other mutations had elevated average ferritin levels, but their TS remained within the reference range. Conclusion The results indicate a high frequency of individuals with genetic alterations in the HFE gene among males and aged between 41 and 60 years, as well as in those with heterozygous C282Y and H63D. The mean TS was higher in individuals homozygous for the C282Y mutation, with a statistically significant difference, confirming the correlation between genotype and phenotype, leading to iron overload in the organs. In this group, the mean ferritin values were higher compared to the other groups, but without a statistically significant difference. This retrospective study, covering 5 years, may contribute valuable information regarding the genetic profile of the population affected by HH, with updated frequency data.