Histocompatibility antigens as markers of abnormal iron metabolism in patients with idiopathic haemochromatosis and their relatives
Bomford, A.; Eddleston, A.L.; Kennedy, L.A.; Batchelor, J.R.; Williams, R.
Lancet 1(8007): 327-329
1977
ISSN/ISBN: 0140-6736 PMID: 64857 Document Number: 120219
HLA-A3 was significantly more common in 35 unrelated patients with idiopathic hemochromatosis (69%) than in 95 controls (31%). Further studies in 2 families suggest that 2 genes are involved in the pathogenesis of the disease, each associated with a separate metabolic defect. Whereas minor abnormalities, i.e., raised serum-Fe and some increase in storage Fe were found in relatives with an HLA A11, B27, CW2 haplotype, those with the A3, B14, CW5 haplotype had no detectable abnormalities. When both these haplotypes were found together, as in the propositus and 1 sibling in the 1st family investigated, all the signs of the fully developed disease were apparent. It is suggested that 1 of the genes is in linkage dysequilibrium with HLA-A3 and could be responsible for a kinetic abnormality, possibly increased plasma to storage Fe exchange. The other gene, also carried on the 6th chromosome, and in the 1st family, marked by the HLA A11, B27, CW2 haplotype, might result in an increased absorption of dietary Fe. The concomitant inheritance of these 2 genes and the metabolic defects they determine are required for the full development of the disease.