The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients.
Hepatology
; 24(1): 43-6, 1996 Jul.
Article
em En
| MEDLINE
| ID: mdl-8707280
ABSTRACT
We evaluate the relation between genotype and phenotype in 47 Italian male patients with homozygous genetic hemochromatosis (GH). Phenotype evaluation was based on the ratio of amount of iron removed (IR) by phlebotomy and age (IR/age). Patients were divided in two classes of phenotype expression class I included 26 patients with less severe iron overload (IR/age <0.33) and class II included 21 patients with a more marked one (IR/age >0.33). Genetic variability was assessed by haplotype analysis combining alleles at HLA-B, D6S265, HLA-A, and D6S105 loci. A common ancestral haplotype carrying D6S265-1, HLA-A3, and D6S105-8 alleles was present in 13 of 52 (25%) chromosomes in class I and in 24 of 42 (57%) chromosomes in class II (P = .0027). Homozygotes and heterozygotes for the ancestral haplotype had higher iron indices than patients carrying two haplotypes other than the ancestral one. Seven of the eight patients homozygous for the ancestral haplotype were in class II, heterozygotes were equally distributed between the two classes, whereas 14 of 18 carriers of other haplotype combinations were in class I. Our results suggests that the gene defect linked to the ancestral haplotype is the result of a single, severe mutation. The high variability of phenotype expression in heterozygotes for the ancestral haplotype could be accounted for the contribution of the mutation carried by the second haplotype. Combination of different mutations could be responsible for the variable degrees of iron overload found in patients with GH.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos HLA-A
/
Antígenos HLA-B
/
Hemocromatose
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article