PMID- 17924859
OWN - NLM
STAT- MEDLINE
DCOM- 20071109
LR  - 20211203
IS  - 0902-4441 (Print)
IS  - 0902-4441 (Linking)
VI  - 79
IP  - 5
DP  - 2007 Nov
TI  - The HLA-A1-B8 haplotype hitchhiking with the hemochromatosis mutation: does it 
      affect the phenotype?
PG  - 429-34
AB  - BACKGROUND: Hemochromatosis is a recessively inherited disorder caused by a point 
      mutation, C282Y of the HFE gene on chromosome 6p21.3 near the human leukocyte 
      antigen (HLA) locus. It is unknown why some homozygotes develop a severe iron 
      loading, while others do not. A recent study suggested that the A1-B8 haplotype 
      may be associated with higher iron storage. METHODS: We studied HLA haplotypes of 
      85 probands, 31 females and 54 males, and their family members from a rural 
      population where A1-B8 was common. We tested the hypothesis of a modifying effect 
      of the A1-B8 haplotype. RESULTS: Most homozygotes had a mild phenotypic 
      expression, and were often detected accidentally because of a laboratory routine 
      including transferrin saturation. A disease-related morbidity [serum alanine 
      aminotransferase (S-ALT) > 43 U] was present in 40%. Three had porphyria cutanea 
      tarda. Two brothers with A1-B8 died of bronze diabetes, probably caused by 
      co-inheritance of congenital spherocytosis. In females there were no significant 
      differences in phenotypic expression between groups with regard to the presence 
      or absence of A1-B8. Two females, <50 yr of age, with this haplotype had iron 
      deficiency. Males with two copies of A1-B8 had significantly lower serum ferritin 
      (P = 0.02) values than those without. Those with one A1-B8 haplotype were not 
      different from those without. In men without A1-B8, those carrying HLA-A3 were 
      not phenotypically different from those without this ancestral haplotype. 
      CONCLUSION: The A1-B8 haplotype hitchhiking with the C282Y mutation was not 
      associated with a more efficient iron absorption. On the contrary, males with 
      double copies of this haplotype expressed a milder phenotype, possibly an effect 
      of local (environmental and/or genetic) factors.
FAU - Olsson, K Sigvard
AU  - Olsson KS
AD  - Department of Medicine, Sahlgrenska University Hospital, Goteborg, Sweden. 
      sigvard.olsson@medic.gu.se
FAU - Ritter, Bernd
AU  - Ritter B
FAU - Hansson, Norbeth
AU  - Hansson N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (HFE protein, human)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (HLA-A3 Antigen)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 9007-73-2 (Ferritins)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cysteine
MH  - Female
MH  - Ferritins/blood
MH  - HLA-A1 Antigen/*genetics
MH  - HLA-A3 Antigen/genetics
MH  - HLA-B8 Antigen/*genetics
MH  - Haplotypes
MH  - Hemochromatosis/*genetics
MH  - Hemochromatosis Protein
MH  - Histocompatibility Antigens Class I/genetics
MH  - Humans
MH  - Iron Deficiencies
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Middle Aged
MH  - *Mutation
MH  - Pedigree
MH  - Phenotype
MH  - Sweden
MH  - Tyrosine
EDAT- 2007/10/11 09:00
MHDA- 2007/11/10 09:00
CRDT- 2007/10/11 09:00
PHST- 2007/10/11 09:00 [pubmed]
PHST- 2007/11/10 09:00 [medline]
PHST- 2007/10/11 09:00 [entrez]
AID - EJH953 [pii]
AID - 10.1111/j.1600-0609.2007.00953.x [doi]
PST - ppublish
SO  - Eur J Haematol. 2007 Nov;79(5):429-34. doi: 10.1111/j.1600-0609.2007.00953.x.