The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients

被引:51
作者
Piperno, A
Arosio, C
Fargion, S
Roetto, A
Nicoli, C
Girelli, D
Sbaiz, L
Gasparini, P
Boari, G
Sampietro, M
Camaschella, C
机构
[1] CTR AUXOL ITALIANO PIANCAVALLO,MILAN,ITALY
[2] UNIV MILAN,IST MED INTERNA & FISIOPATHOL MED,MILAN,ITALY
[3] UNIV TURIN,DIPARTIMENTO SCI BIOMED & ONCOL UMANA,TURIN,ITALY
[4] UNIV VERONA,IST CLIN MED,VERONA,ITALY
[5] OPSED CSS SAN GIOVANNI ROTONDO,LRCCS,FOGGIA,ITALY
[6] CNR,CIOS,TURIN,ITALY
[7] UNIV CATTOLICA SACRO CUORE,IST STAT,MILAN,ITALY
关键词
D O I
10.1002/hep.510240109
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 less than or equal to 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 suggest 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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页码:43 / 46
页数:4
相关论文
共 18 条
  • [1] VALUE OF HEPATIC IRON MEASUREMENTS IN EARLY HEMOCHROMATOSIS AND DETERMINATION OF THE CRITICAL IRON LEVEL ASSOCIATED WITH FIBROSIS
    BASSETT, ML
    HALLIDAY, JW
    POWELL, LW
    [J]. HEPATOLOGY, 1986, 6 (01) : 24 - 29
  • [2] CONSTRUCTION OF A GENETIC-MAP TELOMERIC TO HLA-A BY MICROSATELLITE ANALYSIS
    CAMASCHELLA, C
    ROETTO, A
    DESANDRE, G
    PIPERNO, A
    TOTARO, A
    DIANZANI, I
    GASPARINI, P
    [J]. MOLECULAR AND CELLULAR PROBES, 1993, 7 (05) : 411 - 414
  • [3] Camaschella C, 1996, HUM GENET, V97, P476
  • [4] MAP OF THE HUMAN MHC
    CAMPBELL, RD
    TROWSDALE, J
    [J]. IMMUNOLOGY TODAY, 1993, 14 (07): : 349 - 352
  • [5] CONCORDANCE OF IRON STORAGE IN SIBLINGS WITH GENETIC HEMOCHROMATOSIS - EVIDENCE FOR A PREDOMINANTLY GENETIC EFFECT ON IRON STORAGE
    CRAWFORD, DHG
    HALLIDAY, JW
    SUMMERS, KM
    BOURKE, MJ
    POWELL, LW
    [J]. HEPATOLOGY, 1993, 17 (05) : 833 - 837
  • [6] CRAWFORD DHG, 1995, AM J HUM GENET, V57, P362
  • [7] *GEN, 1992, GEN MICR MAP CAT
  • [8] JAZWINSKA EC, 1995, AM J HUM GENET, V56, P428
  • [9] SATURABILITY OF HEPATIC IRON DEPOSITS IN GENETIC HEMOCHROMATOSIS
    MANDELLI, C
    CESARINI, L
    PIPERNO, A
    FARGION, S
    FRACANZANI, AL
    BARISANI, D
    CONTE, D
    [J]. HEPATOLOGY, 1992, 16 (04) : 956 - 959
  • [10] EVIDENCE FOR HETEROGENEITY IN HEREDITARY HEMOCHROMATOSIS - EVALUATION OF 174 PERSONS IN 9 FAMILIES
    MUIR, WA
    MCLAREN, GD
    BRAUN, W
    ASKARI, A
    [J]. AMERICAN JOURNAL OF MEDICINE, 1984, 76 (05) : 806 - 814