Linkage disequilibrium between S65C HFE mutation and HLA A29-B44 haplotype in Terceira Island,Azores

Our objective was to investigate the frequency of HFE gene mutations and to study linkage disequilibrium (LD) between HLA-Class I alleles and these mutations in the population of Terceira Island, Azores, Portugal. A total of 218 unrelated individuals were investigated. Three HFE mutations--C282Y, H63D, and S65C--were identified by restriction endonuclease digestion of polymerase chain reaction (PCR)-amplified genomic DNA. HLA-Class I alleles were typed by PCR-single-strand polymorphism. Gene frequencies and LD were estimated using Arlequin V 1.1. Six genotypes were found in the population: WT/WT (58.3%), H63D/WT (31.2%), H63D/H63D (2.3%), H63D/C282Y (0.9%), S65C/WT (4.1%), and C282Y/WT (3.2%). No cases of C282Y or S65C homozygosity were identified. HLA haplotype A3-B7 was in LD with C282Y; HLA alleles A29, B44, and HLA haplotype A29-B44 were in LD with S65C mutation. HFE gene frequencies in this population are similar to those in other European populations; HFE S65C mutation was found in LD with the alleles A29, B44, and with A29-B44 HLA haplotype.     

The role of HFE mutations on iron metabolism in beta-thalassemia carriers

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and progressive storage resulting in organ damage. HFE gene mutations C282Y and H63D are responsible for the majority of HH cases. A third HFE mutation, S65C, has been associated with the development of a mild form of hemochromatosis. The beta-thalassemia trait is characterized by mild, ineffective erythropoiesis that can induce excess iron absorption and ultimately lead to iron overload. The aim of this study was to evaluate the effect of genetic markers (HFE mutations C282Y, H63D, and S65C) on the iron status of beta-thalassemia carriers. A total of 101 individuals heterozygous for beta-thalassemia and 101 normal control individuals were studied. The allelic frequencies of C282Y (1.5 versus 3.5%), H63D (15.3 versus 18.3%), and S65C (1.0 versus 1.5%) did not differ significantly between beta-thalassemia carriers and normal controls. Serum iron (P=0.029) and transferrin saturation (P=0.009) were increased in beta-thalassemia carriers heterozygous for H63D mutation. The number of subjects carrying C282Y or S65C mutations was too low to conclude their effect on the iron status. These results suggest that the beta-thalassemia trait tends to be aggravated with the coinheritance of H63D mutation, even when present in heterozygosity.     

Global prevalence of putative haemochromatosis mutations.

Haemochromatosis is a genetic disease associated with progressive iron overload, and is common among populations of northern European origin. HLA-H is a recently reported candidate gene for this condition. Two mutations have been identified, a substitution of cysteine for tyrosine at amino acid 282 (C282Y, nucleotide 845) and of histidine for aspartate at amino acid 63 (H63D, nucleotide 187). Over 90% of UK haemochromatosis patients are homozygous for the C282Y mutation. We have examined 5956 chromosomes (2978 people) for the presence of HLA-H C282Y and H63D by PCR followed by restriction enzyme analysis. We have found world wide allele frequencies of 1.9% for C282Y and 8.1% for H63D. The highest frequencies were 10% for C282Y in 90 Irish chromosomes and 30.4% for H63D in 56 Basque chromosomes. C282Y was most frequent in northern European populations and absent from 1042 African chromosomes, 484 Asian chromosomes, and 644 Australasian chromosomes. The distribution of the C282Y mutation coincides with that of populations in which haemochromatosis has been reported and is consistent with the theory of a north European origin for the mutation. The H63D polymorphism is more widely distributed and its connection with haemochromatosis remains unclear.     

Association between the HFE mutations and longevity: a study in Sardinian population

Hereditary hemochromatosis is an HLA-linked inherited disease characterised by inappropriately high absorption of iron by the gastrointestinal mucosa. The cysteine-to-tyrosine substitution at codon 282 of the HFE encoding gene sequence is responsible for the disease, although other variants, as H63D and S65C, may modify the affinity of the protein for transferrin receptors. We have recently reported that C282Y mutation is significantly increased in very old (>90 years) Sicilian women, suggesting a role in attainment of longevity. In addition, an increase of H63D polymorphism was also observed in these women but the difference was not significant. To validate and extend these results we investigated the distribution of these three common HFE gene mutations in Sardinian centenarians and controls. DNA samples, obtained from 61 controls and 57 Centenarians, were typed for HFE polymorphisms using sequence specific primers. Among the controls, none was heterozygous for the C282Y mutation, 15 were heterozygous for H63D mutation and one for S65C. Among the centenarians, none was heterozygous for the C282Y mutation whereas 25 were heterozygous for H63D mutation and four for the S65C mutation. No significant differences were observed in frequencies of the different alleles between young and centenarians both on the whole and when the data were analysed according to gender. However, there was a trend for an increased frequency of H63D allele in centenarian women (24 vs. 17%, i.e. 19/80 vs. 13/78). It is noteworthy that the cumulative frequency of H63D mutations in Centenarian and very old women from Sardinia and Sicily is 22 vs. 11%, i.e. 30/136 vs. 23/210, P=0.008. These findings are consistent with the hypothesis that there may be a survival difference for centenarian women, among carriers and non-carriers of alleles involved in iron sparing.     

HFE gene mutations analysis in Basque hereditary haemochromatosis patients and controls

C282Y/C282Y genotype is the prevalent genotype in Hereditary Haemochromatosis (HH), however, other genotypes have been associated with the disease. The objective of our study was to analyse the frequency of the three main mutations of HFE gene in HH patients and controls from the Basque population with differential genetic characteristics. Thirty five HH patients and 116 controls were screened for C282Y, H63D and S65C mutations using a PCR-RFLP technique. The association of HLA-A and-B alleles and HFE mutations was also studied in Basque controls. The frequency of C282Y homozygotes in the group of patients was only 57%. The rest of the patients presented heterogeneous genotypes, including compound heterozygotes: 11% of them were C282Y/H63D; and 2.85% were H63D/S65C. H63D or S65C heterozygotes had a frequency of 11% and 2.85 respectively and 5.71% patients lacked any mutation The high frequency of H63D in the healthy Basque population is confirmed in this study. A considerable incidence of S65C is observed either in controls and in HH (3%) or in iron overloaded patients. The peculiar genetic characteristics of Basques could explain the heterogeneity of genotypes in HH patients of this group. Further studies should be carried out to confirm these findings although the implication of other genetic or external factors in the development of HH is suggested.     

Analysis of the HFE gene (C282Y, H63D and S65C) mutations in a general Chinese Han population

Hereditary hemochromatosis (HH) is one of the most common autosomal recessive genetic disorders of iron metabolism in white populations, which leads to inappropriately high iron absorption. C282Y, H63D, and S65C are three major missense mutations of the hemochromatosis gene (HFE). In the present study, C282Y, H63D, and S65C mutations in 395 normal Chinese Han populations from Zhejiang province were investigated. No C282Y, S65C mutations, and H63D homozygote was observed, while the genotype frequency of H63D heterozygote was 4.6% and the allelic frequency 2.3% in this population. This was the first report to analyze the prevalence of C282Y, H63D, and S65C mutations in the HFE gene in a Chinese Han population. Low incidence of the HFE gene mutations could be a reason for the rarity of HH in the Chinese Han population studied.     

Frequency of the Hemochromatosis Gene (HFE) Variants in a Jordanian Arab Population and in Diabetics from the Same Region

Hereditary HFE-linked hemochromatosis is a frequent recessive disorder among individuals of northern European ancestry. The clinical characteristic of this disease is the gradual accumulation of iron in internal organs, which ultimately may lead to organ damage and death. Three allelic variants of HFE gene have been correlated with hereditary hemochromatosis: C282Y is significantly associated with hereditary hemochromatosis in populations of Celtic origin, H63D and S65C are associated with milder form of iron overload. In this study we performed mutation analysis to identify allele frequency of the three variants of HFE gene in Jordanian Arab population, to assess deviations of these frequencies from those detected elsewhere, and to determine if there is an increased frequency of these variants in a diabetic population (Type 2 diabetes) from the same area. DNA was extracted from blood samples of 440 individuals attending King Abdullah University Hospital for ambulatory services. We used polymerase chain reaction (PCR) to amplify exons 2 and 4 of the HFE gene then restriction fragment length polymorphism (RFLP) method to detect the variants. There were neither homozygous nor heterozygous for C282Y variant. For the H63D variant, 0.68% were homozygous and 21.1% were heterozygous. For the S65C variant, there were no homozygous and 0.23% were heterozygous. Allelic frequencies were, 0%, 11.25%, and 0.11% for C282Y, H63D, and S65C, respectively. Our samples were subdivided into two categories of type 2 diabetic (89 cases) and controls (blood donors, 204 cases) and compared with regard to the H63D variant. Both groups did not have homozygous H63D variant. H63D heterozygous in diabetics were 23.60% and in blood donor controls 22.55%. Allelic frequency of the mutant H63D allele was 11.80% in diabetics and 11.27% for the blood donor controls. This is the first study to show the frequency of the three hemochromatosis gene variants in Jordan with the interesting finding of no C282Y allele detected in 440 samples. Additionally, no significant difference was observed in H63D variant frequency in type 2 diabetics as compared to controls.     

A 6-year survey of HFE gene test for hemochromatosis diagnosis.

PURPOSE: A 6-year survey of HFE gene test was conducted to evaluate its helpfulness for hereditary hemochromatosis diagnosis. METHODS: We analyzed C282Y, H63D, and S65C mutations on 3525 individuals. RESULTS: The test produced 89.7% and 30% of positive results for individuals clinically diagnosed hemochromatosis before HFE gene-test availability and those prospectively tested because of elevated serum iron parameter and/or family history, respectively; among them there were 90.4% and 48.7% of C282Y homozygotes. CONCLUSIONS: The HFE gene test confirmed a genetic defect that may lead to iron loading in individuals when iron parameter values, especially for the C282Y/C282Y, were still low as well as for genotypes usually associated with low expressivity and penetrance (C282Y/H63D, H63D/H63D). This gene-test should allow a biochemical follow-up of patients carrying a disease-related genotype.     

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population

Classes I and II human leukocyte antigens (HLA) genes encode highly polymorphic heterodimeric glycoproteins involved in the control of immune responses. The HLA class I gene HFE seemingly no longer participates in immunity because it has lost its ability to bind peptides and it has acquired the ability to form complex with the receptor for iron-binding transferrin by regulating iron uptake by intestinal cells. Thus, it indirectly regulates immune responses too, because iron availability plays a role in specific and non-specific immune responses. The distribution of HFE polymorphisms in Sicilian centenarians and nonagenarians was studied to evaluate if HFE alleles might be represented differently in people selected for longevity. DNA samples were obtained from 106 young controls (age range from 22 to 55 years; 40 men and 66 women) and 35 elderly subjects (age range from 91 to 105 years; seven men and 28 women). Samples were typed for C282Y, H63D and S65C alleles using polymerase chain reaction and sequence specific primers. Among the young individuals, none was heterozygous for the C282Y or for S65C mutation. Twenty-six were heterozygous for H63D mutation. Among the elderly subjects, 11 were heterozygous for the C282Y mutation or for H63D mutation. None was heterozygous for the S65C mutation. No compound heterozygous individuals (C282Y/H63D) were found. A highly significant difference was observed in frequencies of C282Y alleles between the young and the elderly subjects on the whole. By analysing polymorphisms according to gender, heterozygous subjects for C282Y were found both in old men and in old women, but by comparing the allele frequencies to those of young people significance was attained only in women. Concerning H63D polymorphisms, no significant differences were observed, between old and young people, both in men and in women. Possession of C282Y allele, known to be associated with an increase of iron uptake, significantly increases women possibility to reach longevity. Thus, present data adds another piece of evidence to the complex puzzle of genetic and environmental factors involved in control of lifespan expectancy in humans.     

Molecular diagnosis of hereditary hemochromatosis: application of a newly-developed reverse-hybridization assay in the South African population

A recently developed strip-assay for hemochromatosis provides a rapid method for simultaneous detection of multiple mutations, which among others includes the HFE gene mutations V53M, V59M, H63D, H63H, S65C, Q127H, E168Q, and C282Y, previously detected in the general South African population using gel-based mutation-screening methods. The objective of the study was to determine the frequency of the relatively rare mutations in samples selected for altered iron parameters or a family history of hereditary hemochromatosis (HH) as part of the validation process of the assay for routine diagnostic purposes. The study population consisted of 451 individuals previously screened for mutations C282Y and H63D by restriction enzyme analysis in order to confirm or possibly exclude a diagnosis of HH. These individuals were subjected to mutation screening using the commercially available hemochromatosis strip-assay. Previous positive results for mutations C282Y and H63D in 233 individuals confirmed the accuracy of the reverse-hybridization assay. Mutation S65C was detected in 13 Caucasians, including three compound heterozygotes. These constituted 2% (13/600) of the chromosomes without mutations C282Y or H63D. The African-specific HFE mutation V53M was detected in one out of 11 (9%) African subjects screened. Mutation E168Q was detected in a single Caucasian individual together with mutation H63D. Our data demonstrate the value of the strip-based technology in providing a rapid and reliable comprehensive test for simultaneous analysis of multiple mutations.     

Frequencies of C282Y and H63D alleles in the HFE gene among various Jewish ethnic groups in Israel: A change of concept required

PurposeHereditary hemochromatosis has not been fully evaluated in the non-Ashkenazi population and is considered to be relatively rare. After ascertaining three unrelated hereditary hemochromatosis families of North African Jewish origin with the HFE C282Y/C282Y genotype, we evaluated the C282Y and H63D allele frequencies among the different Jewish ethnic groups in Israel, in particular North African Jews.MethodsData were collected from three Israeli Medical Centers. North African, Oriental, Yemenite, and Sephardic Jewish healthy individuals were assessed for the C282Y and H63D alleles.ResultsThe C282Y allele frequency was 1.02% (6/586 chromosomes), and the H63D allele frequency was 13.82% (81/586 chromosomes) in the North African Jewish group. The C282Y allele was not detected in the other non-Ashkenazi groups. The H63D allele frequency was 12.5% (38/304 chromosomes) in Oriental Jews, 14.9% (14/94 chromosomes) in Yemenite Jews, and 9.3% (11/118 chromosomes) in Sephardic Jews.DiscussionHereditary hemochromatosis is underrecognized among North African Jews, who have carrier frequencies of 1/58 and 1/4 for C282Y and H63D, respectively. HFE-hereditary hemochromatosis is not rare among this population as currently thought and merits increased awareness to prevent endpoint disease. The frequent occurrence of β-thalassemia trait and HFE-H63D in non-Ashkenazi Jews raises the possibility of genetic interactions contributing to iron overload when coinherited and requires further evaluation.     

Simultaneous detection of HFE C282Y, H63D and S65C mutations associated with type 1 haemochromatosis using a multiplex luminex bead assay

Type 1 hereditary haemochromatosis (HH) is a common genetic disorder in Caucasoids resulting from mutations in the HFE gene. Routine diagnostic testing for type 1 HH involves genotyping for two of these described HFE mutations, C282Y and H63D. In some cases typing of a third mutation, S65C is also performed. Several techniques have been reported for HFE genotyping and these include polymerase chain reaction (PCR)-sequence-specific primers (SSP), PCR-restriction fragment length polymorphism (RFLP), PCR-sequence-specific oligonucleotide probe (SSOP), real-time PCR followed by melting curve analysis and TaqMan assay. The aim of this study was to develop an alternative method to both conventional PCR and real-time PCR/TaqMan assay to detect all three HFE mutations in a single assay using Luminex technology. DNA controls of known genotypes (n = 109) were used to evaluate this approach. These controls were selected to represent the three possible genotypes (wild type, mutant, heterozygous) for each mutation. Subsequently, blind DNA samples (n = 100) were used to validate this method. This new assay was then compared with current techniques (in-house PCR-SSP and TaqMan assay). Comparison of genotypes obtained with the Luminex method with those previously reported by both in-house PCR-SSP and TaqMan assay showed 100% concordance for both DNA controls and blind DNA samples and no discrepancies were observed. Allelic frequency for C282Y, H63D and S65C mutations were 22%, 16% and 2%, respectively. We report here a high-throughput, accurate and robust multiplex luminex bead assay for routine clinical testing of C282Y, H63D and S65C mutations in the HFE gene.     

A previously undescribed frameshift deletion mutation of HFE (c.del277; G93fs) associated with hemochromatosis and iron overload in a C282Y heterozygote

A 62-year-old white man with a hemochromatosis phenotype was found to be heterozygous for the C282Y mutation of the HFE gene. The H63D and S65C mutations of HFE were not present. As most C282Y heterozygotes do not develop a hemochromatosis phenotype, the coding region of the patient's HFE gene was sequenced and a previously undescribed frameshift mutation was identified in exon 2 (c.del277; G93fs) that resulted in a premature stop-codon. There were no coding region mutations of the ferroportin gene (FPN1). We performed human leukocyte antigen (HLA) typing of the patient and his brother who was heterozygous for the C282Y HFE mutation unassociated with a hemochromatosis phenotype. They shared only C282Y and the HLA haplotype A*03, B*14; hence, the c.del277 mutation was linked to the HLA haplotype A*02, B*44 and therefore not on the same chromosome as the C282Y mutation. Thus, the present patient's only intact HFE protein is C282Y, and this may explain his hemochromatosis phenotype.     

Hemochromatosis and transferrin receptor gene polymorphisms in chronic hepatitis C: impact on iron status, liver injury and HCV genotype

Mild iron overload in chronic hepatitis C is associated with liver fibrosis, hepatitis C virus (HCV) genotype 1b infection, and an impaired response to interferon therapy. In this study we evaluated whether polymorphisms in the hemochromatosis gene HFE and the transferrin receptor gene TFR1 are associated with these typical findings. The study considered 246 HCV-infected patients and 200 blood donors as controls, in which C282Y, H63D, and S65C mutations (HFE) and the S142G polymorphism (TFR1) were detected. HCV genotype, serum ferritin levels, stainable intrahepatic iron, and grade of fibrosis according to the METAVIR score (F0–F4) were determined. In HCV-infected patients, heterozygosity for the C282Y mutation in HFE was significantly associated with elevated serum ferritin levels, stainable liver iron, and advanced fibrosis or cirrhosis (F2–F4). By multivariate logistic regression analysis the odds ratio for the development of advanced fibrosis or cirrhosis (F2–F4) was 2.5 for HCV-infected patients carrying a heterozygous C282Y mutation and 4.8 for HCV-infected patients with C282Y/H63D and C282Y/S65C compound heterozygosity. Heterozygosity for the C282Y mutation in HFE contributes to iron accumulation and fibrosis progression in chronic hepatitis C.Abbreviation HCV Hepatitis C virus     

C282Y and H63D Mutation Frequencies in a Population from Central Spain

Objectives: To determine the frequency of hereditary hemochromatosis gene mutations, C282Y and H63D, from 125 autochthonous blood donors originating from a Central region of Spain, to provide epidemiological data about HFE gene in the Iberian Peninsula. Methods: DNA extracted from blood samples was analyzed by PCR-RFLP. Restriction enzimes were Snab I and Bcl I for C282Y and H63D, respectively. Results were visualized with Ethidium Bromide staining after gel electrophoresis. Results and discussion: C282Y frequency was 0.02 and that of H63D was 0.16. Result for C282Y mutation falls within the range of variation of the Mediterranean populations. H63D frequency agrees with those reported for other European populations. In both cases frequencies obtained are the lowest of compared Spanish data. Conclusions: This study is useful to compare expected versus presented C282Y and H63D frequencies in Spanish populations and to contribute to the knowledge of Spanish variability, rarely analyzed until now for HFE gene mutations.     

Association between the HFE mutations and unsuccessful ageing: a study in Alzheimer's disease patients from Northern Italy

Mutations in the class I-like Major Histocompatibility Complex gene HFE are associated with hereditary hemochromatosis (HH), a disorder caused by excessive iron uptake. Three common mutations have been found: C282Y, H63D, and S65C. Moreover, several studies have suggested that HFE mutations may be involved in several age-related chronic diseases such as Alzheimer's disease (AD) and coronary heart disease, but apparently paradoxically also with longevity. In particular, in AD, patients carrying the H63D allele have been suggested to have a mean age at onset of 72 vs. 77 years for those who were homozygous for the wild-type allele. Thus, it seems that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals. In the present study, we analysed the HFE genotype in 123 patients with sporadic AD and 152 age-matched controls from Northern Italy. Samples were typed for C282Y, H63D and S65C alleles using the polymerase chain reaction and sequence specific primers. No significant differences were observed in frequencies of the different alleles between controls and AD both for the whole group and when the data were analysed according to gender. In addition, we failed to observe any difference in the age at onset between patients carrying the mutant HFE-H63D allele and those homozygous for the wild-type allele, either in men or women. Also taking into account the presence or absence of the APOE-epsilon 4 allele, no significant differences were observed between carriers of the mutant HFE-H63D allele and those homozygous for the wild-type allele. Thus, our study does not support the suggestion that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals.     

HFE genotypes in patients with chronic pancreatitis and pancreatic adenocarcinoma

PurposeThe homozygous p.C282Y variant of the HFE gene is a major risk factor for hereditary hemochromatosis, a disorder of iron metabolism resulting in progressive iron accumulation in a variety of organs including the pancreas. Heterozygosity of p.C282Y and p.H63D may increase susceptibility to chronic liver and pancreatic disease. This study determines the frequencies of p.C282Y and p.H63D alterations in patients with chronic pancreatitis and pancreatic adenocarcinoma.MethodsIn total, 958 patients (349 with alcoholic pancreatitis, 343 with idiopathic pancreatitis, 64 with familial chronic pancreatitis, 34 with acute pancreatitis, and 168 with pancreatic adenocarcinoma) were enrolled and compared with 681 healthy and 100 alcoholic controls. Furthermore, 45 parent–offspring trios were included for segregation analysis. Genotyping of p.C282Y and p.H63D was performed by restriction fragment length polymorphism or melting curve analyses.ResultsNo significant differences were found in heterozygosity for p.C282Y and p.H63D when patients with alcoholic (8.0/21.5%), idiopathic (7.3/24.5%), or familial (9.8/23.0%) pancreatitis, or pancreatic adenocarcinoma (5.4/28.6%) were compared with healthy (6.2/24.8%) and alcoholic (7.0/25.0%) controls. Neither genotype was associated with the presence of secondary diabetes mellitus in patients with chronic pancreatitis.ConclusionAlthough hemochromatosis is associated with pancreatic pathology, the p.C282Y and p.H63D variants do not play a significant role in the pathogenesis of chronic pancreatitis or pancreatic adenocarcinoma.     

Relation between HFE mutations and mild iron-overload expression

The identification of the HFE gene involved in hemochromatosis allows genetic tests based on mutation analysis to be performed. However, discrepancies in the correlation between HFE genotypes and iron-loading status have arisen. We investigated 708 patients with various signs or symptoms suggesting a putative iron overload that, nevertheless, did not reach the current criteria for hemochromatosis diagnosis. Most of the patients (91.4%) included in our study displayed one of three classical iron marker values above the threshold defined for iron overloading. HFE mutation analysis allowed us to identify 45.7% of carrier chromosomes in the studied group of patients that showed higher frequencies of HFE mutations compared with controls. In addition, the frequencies of compound C282Y/H63D heterozygous, H63D/H63D homozygous, and C282Y heterozygous genotypes were higher than those in HH probands and controls; they accounted for 16, 5.6, and 22.5% of the patients, respectively. All genotypic groups had a significantly higher value of serum ferritin concentration compared to the normal value; only the C282Y homozygotes and compound heterozygotes with H63D had a transferrin saturation significantly higher than the normal value. On the whole the H63D homozygous and compound heterozygous patients constitute an intermediate phenotypic group between HH and controls. Some of them may reach the critical overloading defined for HH diagnosis along with a potential risk of developing complications, whereas others only show a partial phenotypic expression.     

Iron overload and HFE gene mutations in Czech patients with chronic liver diseases

The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.     

HFE蛋白与遗传性血色病

遗传性血色病(hereditary haemochromatosis,HH)是一种遗传性铁代谢疾病。发病遍及全球,以白种人发病较多,北欧人群发病率可高达1/200。大约1/10的白色人种是HFE突变基因携带者[1]。国内对HH的发病率尚无确切统计数字,但全国各地均有病例报道[2]。HH主要特征为小肠铁吸收过量增加,逐渐在肝、心、胰和其它内分泌器官的实质细胞沉积,造成器官功能障碍、肝硬化、心力衰竭、糖尿病、垂体功能减退和关节疾病等。此种疾病首次报道於1865年,当时认为HH是糖尿病的一种特殊病例。尔后将这类疾病称为色素性肝硬化(pigment cirrho-sis),或古铜色糖…