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ABSTRACT: A new glucose-6-phosphate dehydrogenase variant detected in an Italian man from the Po delata is described and designated as G6PD Modena. Biochemical characterization of the variant enzyme revealed an activity 21% of normal, a slow electrophoretic mobility, increased Km value for NADP, decreased Km value for G6P and a complete absence of NADPH inhibition, which could account for the apparently nonhaemolytic feature of this variant. The cloning and sequencing of the G6PD Modena allele showed a GC transition at nucleotide 844 in exon VIII causing a Asp His amino acid substitution. On the basis of biochemical characterization, G6PD Modena is classified as a genuine variant but it has the same mutation as G6PD Seattle-like.
British Journal of Haematology 03/2008; 87(1):209 - 211. · 4.94 Impact Factor
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British Journal of Haematology 03/2005; 104(4):928 - 929. · 4.94 Impact Factor
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Claudio Velati,
Eugenia Marlianici,
Danila Rigamonti,
Giovanni Barillari,
Francesco Chiavilli,
Paolo Fugiani,
Giovanni Garozzo,
Mario Lancieri,
Sandro Rinaldi,
Domenico Testa, Maurizio Sampietro,
Dario Tavazzi,
Paola Delbini,
Silvia Fargion,
Gemino Fiorelli
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ABSTRACT: The aim of this study was to analyze the role of HFE mutations in blood donors with iron parameters suggesting iron overload, taking into account the regional distribution of HFE mutations in Italy. We studied 5880 subjects undergoing evaluation for blood donation eligibility, from different areas of Italy. Abnormal iron parameters were defined as transferrin saturation (TS) >50% or >45% and serum ferritin (SF) >300 or >250 microg/ml in males and females, respectively. Subjects with increased TS and/or SF were re-tested and typed for HFE mutations C282Y and H63D. A total of 548 individuals had increased iron parameters at first testing. In total, 179/548 were available for retesting, and in 109 increased TS and/or SF were confirmed. Increased TS was confirmed in 25 individuals, among whom three were C282Y homozygotes and six were compound heterozygotes for C282Y and H63D. Increased TS was more frequent in northern Italy than in southern regions. In individuals with increased TS and/or SF, the frequency of C282Y and H63D was 0.13 and 0.21 in northern-Italy versus 0.05 and 0.45 in southern Italy (P=0.004 for H63D). Nine out of 10 individuals carrying hemochromatosis-associated genotypes (including compound heterozygosity for C282Y and H63D) originated from northern regions. Among controls, the allelic frequencies of C282Y and H63D were 0.037 and 0.16 in the northern regions and 0.015 and 0.16 in the southern regions. In conclusion, over one-third of individuals with persistently altered TS carried hemochromatosis-associated genotypes, confirming that a diagnostic approach based on TS and genotyping of selected cases may represent a viable screening procedure.
The Hematology Journal 02/2003; 4(6):436-40. · 1.86 Impact Factor
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ABSTRACT: OBJECTIVE: The aim of this study was to define in patients with hyperferritinemia and normal transferrin saturation the relationships among hyperferritinemia, iron overload, HFE gene mutations, the presence of metabolic alterations, and nonalcoholic steatohepatitis (NASH).
The American Journal of Gastroenterology 07/2001; 96(8):2448-2455. · 7.28 Impact Factor
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Alberto Piperno,
Raffaella Mariani,
Cristina Arosio,
Anna Vergani,
Sandra Bosio,
Silvia Fargion, Maurizio Sampietro,
Domenico Girelli,
Mirella Fraquelli,
Dario Conte,
Gemino Fiorelli,
Clara Camaschella
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ABSTRACT: Severe iron overload has been reported in patients with the β-thalassaemia trait. Studies performed before the discovery of the haemochromatosis gene (HFE) have yielded conflicting results: some suggest that iron overload might arise from the interaction of the β-thalassaemia trait with heterozygosity for haemochromatosis, some with homozygosity for haemochromatosis and others that it was unrelated to haemochromatosis. We have studied the clinical phenotype, iron indices and HFE genotypes of 22 unrelated patients with the β-thalassaemia trait and haemochromatosis, the inheritance of chromosome 6p and 1q haplotypes in families of non-homozygous C282Y probands and serum measures of iron status in relatives heterozygous for C282Y with or without the β-thalassaemia trait. We demonstrate that the β-thalassaemia trait aggravates the clinical picture of C282Y homozygotes, favouring higher rates of iron accumulation and the development of severe iron-related complications. We suggest that the coexistence of the β-thalassaemia trait might also increase the risk of iron overload in patients with HFE genotypes at a mild risk of haemochromatosis. Our findings do not support the hypothesis that the association of the β-thalassaemia trait with a single C282Y or H63D allele might lead to iron overload and suggest that other non-HFE-related inherited factors are present in haemochromatosis patients with incomplete HFE genotypes.
British Journal of Haematology 11/2000; 111(3):908 - 914. · 4.94 Impact Factor
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ABSTRACT: Carbohydrate-deficient transferrin(CDT) a microheterogeneous form of serum transferrin (Tf) has been proposed as the most reliable marker of chronic alcohol consumption, although unexplained false-positive and -negative results have been reported.We investigated whether body iron influenced CDT serum levels by studying alcohol abusers with or without iron overload and nonabusers with iron deficiency or iron overload caused by genetic hemochromatosis (GH).In alcohol abusers, CDT was significantly lower in the presence of iron overload than in the absence (24.6 ±16.5 U/L vs.33.3 ±11.7 U/L; P<.01) with false-negative results almost exclusively in patients with iron overload. Similarly, in nonabusers with GH, CDT was lower than in normal controls (9.6±2.2 U/L vs.15.7 ± 3.3 U/L;P<.0001) whereas, patients with iron deficiency anemia had significantly higher levels than controls (28.1±5.8 U/L vs.15.7±3.3 U/L;P<.0001).In nonabusers, iron supplementation therapy significantly decreased CDT levels in patients with iron deficiency anemia (33.7±6.6 U/L vs.21.7± 5.2 U/L;P=.0007) while iron-depletion treatment significantly increased CDT levels in patients with GH (9.7 ± 2.0 U/L vs. 14.7 ± 4.0 U/L;P=.001).Alcohol abusers had a significant relationship between liver iron concentration (LIC)and the reciprocal of CDT (r=.65;P <.0001) while in nonabusers, there was a significant correlation between Tf and CDT (r=.72;P<.0001).In conclusion, CDT serum levels are markedly affected by the patient's iron status, with iron overload reducing its sensitivity in alcohol abusers and iron deficiency its specificity in nonabusers. CDT can be considered a reliable marker of alcohol abuse only when iron stores are normal.
Hepatology 02/1999; 29(3):658 - 663. · 11.66 Impact Factor
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ABSTRACT: The risk of polytransfused patients for hepatitis C virus (HCV) infection is likely to extend to another recently identified member of the Flaviviridae, hepatitis G virus (HGV). We investigated the prevalence of HGV in 40 adult Italian patients with transfusion-dependent thalassaemia and evaluated the clinical significance of HGV infection. HGV-RNA was detected in 9/40 patients (22.5%). HGV infection was significantly associated with HCV viraemia (P =0.0012), with all patients positive for HGV being also viraemic for HCV. Overall, the clinical picture of patients with HCV/HGV co-infection was not different from that of patients with isolated HCV. However, patients co-infected with both viruses had lower values of alanine-transferase (P =0035) and a lower titre of HCV viraemia (P =0042) in the absence of other evident factors which could influence the clinical expression of HCV infection. In conclusion, HGV is highly prevalent among Italian polytransfused patients. No evidence of a clinically significant pathogenic role for HGV in liver disease could be found in these patients. In a subset of cases a possible interference of HGV with HCV infection was observed.
British Journal of Haematology 05/1997; 97(4):904 - 907. · 4.94 Impact Factor
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Alberto Piperno, Maurizio Sampietro,
Roberta D'Alba,
Luigi Roffi,
Silvia Fargion,
Stefania Parma,
Carlo Nicoli,
Noemi Corbetta,
Massimo Pozzi,
Valeria Arosio,
G. Boari,
Gemino Fiorelli
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ABSTRACT: We studied 81 patients with chronic hepatitis C to investigate the relationship between iron and α-interferon response. Sixty-one patients (group A) were given α-interferon irrespective of iron status, whereas 20 (group B) with iron overload, were iron depleted before α-interferon therapy. In group A, 21 patients responded to α-interferon and 40 were non-responders. Increased iron indices were significantly more frequent in non-responders than responders. Multivariate analysis showed that among the independent variables evaluated, only γ-GT and liver iron concentration predicted therapy outcome. After phlebotomy treatment, serum alanine aminotransferase fell significantly both in patients of group B (196±122 IU/1 vs 82±37 IU/1, p<10-6) and in 12 non-responders of group A (198±89 IU/1 vs 107±81 IU/1, p<10-6). In 16 iron depleted patients, eight from each group, subsequent treatment with α-interferon produced a response in only one patient. These results suggest that increased liver iron is a negative prognostic factor for a-interferon response in chronic hepatitis C. Iron depletion had a beneficial effect on serum alanine aminotransferase in all the patients treated, but did not improve the response to α-interferon.
Liver International 07/1996; 16(4):248 - 254.
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ABSTRACT: The cloning and sequencing of the normal glucose-6-phosphate dehydrogenase (G6PD) gene has led to the study of the molecular defects that determine enzymatic variants. In this paper, we describe the mutations responsible for the Ferrara I variant in an Italian man with a family history of favism, from the Po delta. Nucleotide sequencing of this variant showed a GA mutation at nucleotide 202 in exon IV causing a ValMet amino acid exchange, and a second AG mutation at nucleotide 376 in exon V causing an AsnAsp amino acid substitution. Although on the basis of its biochemical properties this variant was classified as G6PD Ferrara I, it has the same two mutations as G6PD A(-), which is common in American and African blacks, and as the sporadic Italian G6PD Matera. The mutation at nucleotide 202 was confirmed by NlaIII digestion of a polymerase chain reaction amplified DNA fragment spanning 109 bp of exon IV. The 109-bp mutated amplified sequence is not distinguishable from the normal sequence in single strand conformation polymorphism analysis.
Human Genetics 01/1994; 93(2):139-142. · 5.07 Impact Factor
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ABSTRACT: Porphyria cutanea tarda in human beings is believed to be due to reduced hepatic uroporphyrinogen decarboxylase activity. However, extrinsic factors such as alcohol abuse and drug intake are required for clinical manifestation of the disease. In addition to typical cutaneous lesions, patients with porphyria cutanea tarda usually have chronic liver disease and moderate iron overload. Of 74 Italian patients with porphyria cutanea tarda, hepatitis C virus antibodies were detected in 76% by enzyme-linked immunoassay and in 82% by recombinant immunoblot assay. Viral genome, studied with nested polymerase chain reaction, was found in the sera of 49 subjects—47 positive and 2 indeterminate on recombinant immunoblot assay. Five percent of the patients were HBsAg-positive, and about 40% had had past hepatitis B contacts. Alcohol abuse was present in 38%. Liver biopsies performed in 42 patients showed chronic persistent hepatitis in 7 patients, chronic active hepatitis in 22 patients, fibrosis in three patients and cirrhosis in 10 patients. Hepatitis C virus antibody was detected in 100% of patients with chronic active hepatitis and in about 80% of all other groups. Alcohol abuse was more frequent in patients with cirrhosis (80%) than in the other groups. In Italian patients with porphyria cutanea tarda, the prevalence of hepatitis C virus infection was very high, comparable to that in non-A, non-B hepatitis and high-risk patient groups. Hepatitis C virus is probably the main pothogenetic factor of the liver disease of patients with porphyria cutanea tarda.
Hepatology 11/1992; 16(6):1322 - 1326. · 11.66 Impact Factor
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ABSTRACT: In the attempt to define the abnormalities responsible for the severe iron overload found in patients with idiopathic hemochromatosis
(IH) we analyzed, in 8 patients with IH and in 7 normal subjects, by using specific cDNA probes, the genes coding for the
main iron-related proteins, i.e., transferrin, transferrin receptor, as well as H and L subunits of ferritin. In all the patients
tested all the probes failed to evidentiate rearranged bands with any of the restriction enzymes employed. These findings
suggest the absence of gross structural alterations of the genes examined. The lack of polymorphic sites recognized by the
restriction enzymes employed in this study within or around the genes examined does not allow to associate a specific gene
with the disease.
International Journal of Clinical & Laboratory Research 06/1987; 17(3):209-214.
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ABSTRACT: The possible role of iron in facilitating the development of liver cancer is still debated. The aims of this study were to define the prevalence of the mutations 845G → A and 187C → G (C282Y and H63D) in the HFE gene associated with hereditary hemochromatosis in Italian patients with hepatocellular carcinoma occurring in cirrhosis and to analyze the interaction between these mutations and other established risk factors for hepatocellular carcinoma. The HFE gene mutations, performed by polymerase chain reaction, were analyzed in 81 patients (63 males, 18 females) with hepatocellular carcinoma. None of the patients had a phenotype compatible with homozygous hereditary hemochromatosis. Interaction between HFE mutations and exogenous risk factors was analyzed by collecting information on alcohol consumption, hepatitis B and C virus infections, and iron status at the time of diagnosis of chronic liver disease. This analysis was performed only in males to rule out gender influence on patients' iron status by using the case-only approach specifically designed to estimate departure from multiplicative risk ratios under the assumption of independence between genotype and environmental exposure. The prevalence of the C282Y mutation was significantly higher in patients with hepatocellular carcinoma than in normal controls (8.6% vs 1.6%, P < 0.03). At univariate analysis, iron overload was significantly associated with both HFE mutations (P < 0.0001), whereas ongoing hepatitis B virus infection was associated with the C282Y mutation (P < 0.05). By multivariate analysis, a trend for an increased risk of being positive for hepatitis virus markers (OR 2.9, CI 95% 0.9–9.5) and of having been alcohol abusers (OR 3, CI 95% 0.7–14) was observed in patients heterozygous for the HFE mutations. These data indicate that the prevalence of the main mutation associated with hereditary hemochromatosis is significantly higher in cirrhotic Italian patients with hepatocellular carcinoma compared to a normal population and suggest that heterozygotes for HFE mutations exposed to hepatitis virus infections or who had been alcohol abusers could have an increased risk of developing cirrhosis and later liver cancer than people without the mutations exposed to the same risk factors.
Blood Cells Molecules and Diseases 27(2):505-511. · 2.35 Impact Factor
