Molecular medicine and hemochromatosis: At the crossroads

Bacon, Bruce R.; Powell, Lawrie W.; Adams, Paul C.; Kresina, Thomas F.; Hoofnagle, Jay H.

doi:10.1016/s0016-5085(99)70244-1

Cited by 271 publications

(211 citation statements)

References 97 publications

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“…Most Caucasian patients with HH are homozygous for the C282Y mutation, while less than 6% of them are compound heterozygotes for C282Y and H63D (10). Indeed, the C282Y mutation is very common in populations of Northern European ancestry, with a frequency of 5 to 10%, but is very rare in other ethnic groups from Asia and Africa.…”

Section: Introductionmentioning

confidence: 99%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

Palácios

Couto

et al. 2002

Braz J Med Biol Res

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The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.

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Section: Introductionmentioning

confidence: 99%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

Palácios

Couto

et al. 2002

Braz J Med Biol Res

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“…Since the discovery of the hemochromatosis gene in 1996, 2 the C282Y mutation of the HFE gene has been found to be present in more than 90% of typical hemochromatosis patients. 3 The aims of the present study were to determine the prevalence of hemochromatosis using the genetic test, and to study the optimal population screening strategy for hemochromatosis by comparing (1) an established biochemical iron test, the TS, (2) a low-cost alternative iron test, the unbound iron-binding capacity (UIBC), and (3) C282Y genotyping.…”

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confidence: 99%

Population screening for hemochromatosis: A comparison of unbound iron-binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors

et al. 2000

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Early diagnosis and treatment of hemochromatosis is essential to prevent organ damage. Screening strategies to detect early hemochromatosis include testing for iron overload and/or genetic testing. Voluntary blood donors numbering 5,211 were screened with unbound iron-binding capacity (UIBC), transferrin saturation (TS), and genetic testing for the C282Y mutation of the HFE gene. The study found 16 C282Y homozygotes (1 in 327), 69 compound heterozygotes, 371 simple heterozygotes, and 4,755 normals. There were 5 men and 11 women homozygotes with a mean age of 42, range 28 to 57. Mean UIBC (24 ؎ 7 mol/L) and TS (48% ؎ 17%) in homozygotes were significantly different from compound heterozygotes, simple heterozygotes, and normals (ANOVA). Only 3 homozygotes had an elevated serum ferritin. Family studies found an additional 4 iron-loaded homozygotes. Optimal thresholds were Յ28 mol/L for UIBC and Ն46% for TS. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for UIBC of 0.93 (0.85-1.0, 95% confidence interval), and for TS of 0.83 (0.7-0.95). Screening with UIBC to preselect those for genotyping is a cost-efficient strategy for population screening for hemochromatosis.

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“…EREDITARY hemochromatosis is a common inherited disorder of iron metabolism. [1][2][3][4] Recently, a new major-histocompatibility-complex class I-like candidate gene ( HFE ) for hereditary hemochromatosis containing two missense mutations was identified on chromosome 6. 5 A single mutation (G to A at nucleotide 845) in the HFE gene results in the substitution of tyrosine for cysteine at amino acid 282 and is termed the C282Y mutation.…”

Section: Resultsmentioning

confidence: 99%

A Population-Based Study of the Clinical Expression of the Hemochromatosis Gene

1999

N Engl J Med

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Molecular medicine and hemochromatosis: At the crossroads

Cited by 271 publications

References 97 publications

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Population screening for hemochromatosis: A comparison of unbound iron-binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors

A Population-Based Study of the Clinical Expression of the Hemochromatosis Gene

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