ABSTRACT
We initiated the present work to determine whether the presence of the HFE C282Y or H63D mutations could be related to the clinical expression of diabetes mellitus type 2. Two hundred and twenty five type 2 consecutive diabetic patients were included and the HFE genotypes were determined. Younger ages of onset of diabetes as well as a longer duration of the disease were detected in patients carrying at least one C282Y allele (p = 0.007). An increased prevalence of retinopathy (p = 0.014) and of nephropathy (p = 0.04) were also detected in individuals carrying at least one C282Y allele in comparison with patients carrying the other alleles. The increased prevalence of retinopathy in C282Y carriers is related to the increased duration of the disease, but we not have detected that the prevalence of nephropathy is associated with the duration of the disease. However, multivariate logistic regression confirms that the prevalence of nephropathy is higher in the group of patients carrying at least one C282Y allele or the H63D/H63D genotype as compared to the group of patients with the wild-type (N/N) or the N/H63D genotype. To our knowledge our study is the first one to report an earlier age of onset in type 2 diabetic patients carrying HFE mutations.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , Histocompatibility Antigens Class I/genetics , Membrane Proteins/genetics , Age Factors , Age of Onset , Alleles , Analysis of Variance , DNA/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetic Nephropathies/epidemiology , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/genetics , Female , Genetic Predisposition to Disease , Genotype , Hemochromatosis Protein , Humans , Logistic Models , Male , Middle Aged , Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Time FactorsABSTRACT
BACKGROUND/AIMS: Hereditary hemochromatosis is associated with homozygosity for C282Y mutation in the HFE gene, elevated serum transferrin saturation and excess iron deposits throughout the body. We conducted a population-based study in Spain to asses the prevalence of the HFE mutations and their effect on iron parameters. METHODS: We screened 5370 blood donors for the C282Y and H63D HFE mutations by allele-specific polymerase chain reaction. Serum iron, serum ferritin and transferrin saturation were also measured. RESULTS: We have found eight (five men and three women) blood donors who are C282Y homozygotes (0.15%) and 74 C282Y/H63D compound heterozygotes (1.38%). Four out of the eight C282Y homozygotes, all men, had high serum ferritin and transferrin saturation values. No woman was detected with both iron parameters increased. Only one of the 74 C282Y/H63D compound heterozygotes showed elevated serum ferritin and transferrin saturation values (penetrance 1.35%). Serum ferritin and transferrin saturation were significantly higher in C282Y homozygous men as compared with the rest of the genotypes. CONCLUSIONS: The C282Y/C282Y genotype frequency in Spain is 1 in 1004. The C282Y/C282Y genotype is clearly associated with an increase in iron parameters. Biochemical expression of the disease was found in 80% of the C282Y/C282Y men.
