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The HLA-A1-B8 haplotype hitchhiking with the hemochromatosis mutation: does it affect the phenotype?
Eur J Haematol. 2007 Nov; 79(5):429-34.EJ

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. sigvard.olsson@medic.gu.seNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17924859

Citation

Olsson, K Sigvard, et al. "The HLA-A1-B8 Haplotype Hitchhiking With the Hemochromatosis Mutation: Does It Affect the Phenotype?" European Journal of Haematology, vol. 79, no. 5, 2007, pp. 429-34.
Olsson KS, Ritter B, Hansson N. The HLA-A1-B8 haplotype hitchhiking with the hemochromatosis mutation: does it affect the phenotype? Eur J Haematol. 2007;79(5):429-34.
Olsson, K. S., Ritter, B., & Hansson, N. (2007). The HLA-A1-B8 haplotype hitchhiking with the hemochromatosis mutation: does it affect the phenotype? European Journal of Haematology, 79(5), 429-34.
Olsson KS, Ritter B, Hansson N. The HLA-A1-B8 Haplotype Hitchhiking With the Hemochromatosis Mutation: Does It Affect the Phenotype. Eur J Haematol. 2007;79(5):429-34. PubMed PMID: 17924859.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The HLA-A1-B8 haplotype hitchhiking with the hemochromatosis mutation: does it affect the phenotype? AU - Olsson,K Sigvard, AU - Ritter,Bernd, AU - Hansson,Norbeth, PY - 2007/10/11/pubmed PY - 2007/11/10/medline PY - 2007/10/11/entrez SP - 429 EP - 34 JF - European journal of haematology JO - Eur J Haematol VL - 79 IS - 5 N2 - 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. SN - 0902-4441 UR - https://www.unboundmedicine.com/medline/citation/17924859/The_HLA_A1_B8_haplotype_hitchhiking_with_the_hemochromatosis_mutation:_does_it_affect_the_phenotype L2 - https://doi.org/10.1111/j.1600-0609.2007.00953.x DB - PRIME DP - Unbound Medicine ER -