S65C and other mutations in the haemochromatosis gene in the Czech population.

Center of Biomedical Sciences, Division of Cell and Molecular Biology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
Folia biologica (Impact Factor: 0.78). 02/2005; 51(6):172-6.
Source: PubMed

ABSTRACT HFE-linked hereditary haemochromatosis is a common autosomal recessive disease among Caucasians. The primary pathogenetic mechanism is excessive absorption of iron, which is deposited in various organs with their subsequent damage. In 1996 the gene responsible for haemochromatosis was detected--the HFE gene and its major mutation C282Y. The discovery of further mutations followed. Two sites of point mutations in the HFE gene, C282Y and H63D, are associated with more than 80% of haemochromatosis cases. Another mutation-- S65C--was detected on 8% of chromosomes of haemochromatosis patients, which were negative for mutations C282Y or H63D. The objective of this study was to identify the allele frequency of S65C and other HFE mutations in the Czech population. DNA extracted from 481 randomly selected newborn screening cards (Guthrie cards) from all over the country was analysed by PCR-RFLP. No (0%) sample was identified as homozygous for S65C or C282Y mutation and 8 (1.67%) were homozygous for H63D mutation. Twelve (2.49%) samples were S65C heterozygous, 33 (6.86%) samples were C282Y heterozygous, and 128 (26.61%) were H63D heterozygous. Of these, 11 (2.29%) carried one copy of each mutation, i.e. were compound heterozygous. Two samples were S65C/H63D compound heterozygous and nine were C282Y/H63D compound heterozygous. Allele frequencies for S65C, C282Y, and H63D were 1.25% (95% CI, +/- 0.70), 3.43% (95% CI, +/- 1.15), and 14.97% (95% CI, +/- 2.25), respectively. The observed genotype frequency for S65C, C282Y, and H63D mutations in the Czech Republic agrees with those reported for other Central European populations.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The HFE gene mutations play a significant role in the development of hereditary hemochromatosis, which is a disorder of iron metabolism characterised by tissue iron overload. It is also one of the most common genetic diseases among Caucasians. Material and methods In the current study, the frequencies of common single nucleotide polymorphisms in HFE gene [845G→A (C282Y) and 187C→G (H63D)] were estimated in a group of 409 HIV-infected individuals of Caucasian origin from Poland, from which 243 were also HCV-coinfected. TaqMan Real-Time SNP genotyping was performed to screen for the variants. HFE haplotypes and linkage disequilibrium was analysed by the CubeX online tool. Results Frequencies of compound HFE genotypes in the studied population were as follows: 845(GG)–187(CC) – 63.8% (n = 261), 845(GG)–187(CG) – 25.7% (n = 105), 845(GG)–187(GG) – 3.4% (n = 14), 845(GA)–187(CC) – 5.6% (n = 23), 845(GA)–187(CG) – 1.2% (n = 5) and 845(AA)–187(CC) – 0.2% (n = 1). The allele frequencies in HIV-monoinfected were: 845(G) – 95.9%, 845(A) – 4.1%, 187(C) – 81.7%, 187(G) – 18.3% and in HIV/HCV-coinfected: 845(G) – 97.0%, 845(A) – 3.8%, 187(C) – 85.2%, 187(G) – 14.8%. Conclusion Presence of mutations in the HFE gene in the Polish HIV/HCV infected population is similar to those reported for other Caucasian populations. This applies both to the C282Y and H63D variants, although in the second case, recessive allele G appeared numerically more commonly than among other populations tested.
    09/2014; 14(1). DOI:10.1016/j.hivar.2014.08.001
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary hemochromatosis (HH) is a genetic disease caused by the high absorption and deposition of iron in several organs. This accumulation results in several clinical complications such as cirrhosis, arthritis, cardiopathies, diabetes, sexual disorders, and skin darkening. The H63D and C282Y mutations are well defined in the HH etiology. The objective of this article is identification of the H63D and C282Y mutations in the HFE protein gene and the frequency assessment of these mutations in patients with persistent increase of serum ferritin in patients from Natal City from state of Rio Grande do Norte, located in northeastern Brazil. Of the 299 patients studied for C282Y and H63D, 48.49% showed absence of mutation and 51.51% showed some sort of mutation: heterozygous C282Y mutation in 4.35% patients, homozygous C282Y mutation in 2.67% patients, heterozygous H63D mutation in 31.44% patients, homozygous H63D mutation in 8.03% patients, and heterozygous for the mutation in both genes (C282Y/H63D) in 5.02% patients. The S65C mutation was studied in 112 patients and heterozygous mutation (S65D/WT) in 2.67% of patients and double mutation (H63D/S65C) in 1.78% of patients were observed. Due to the high prevalence of hemochromatosis, its genetic diagnosis has become a challenge, especially in the high-risk group.
    Journal of Clinical Laboratory Analysis 01/2014; DOI:10.1002/jcla.21663 · 1.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with alcoholic liver disease (ALD) often display disturbed iron indices. Hepcidin, a key regulator of iron metabolism, has been shown to be down-regulated by alcohol in cell lines and animal models. This down-regulation led to increased duodenal iron transport and absorption in animals. In this study, we investigated gene expression of duodenal iron transport molecules and hepcidin in three groups of patients with ALD (with anaemia, with iron overload and without iron overload) and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in duodenal biopsies by using real-time PCR and Western blot. Serum hepcidin levels were measured by using ELISA. Serum hepcidin was decreased in patients with ALD. At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly increased in ALD. This pattern was even more pronounced in the subgroups of patients without iron overload and with anaemia. Protein expression of FPN1 paralleled the increase at the mRNA level in the group of patients with ALD. Serum ferritin was negatively correlated with DMT1 mRNA. The down-regulation of hepcidin expression leading to up-regulation of iron transporters expression in the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol consumption very probably causes suppression of hepcidin expression in patients with ALD.
    Journal of Cellular and Molecular Medicine 06/2014; DOI:10.1111/jcmm.12310 · 3.70 Impact Factor

Full-text (2 Sources)

Available from
Oct 7, 2014