Idiopathic Hemochromatosis: Linkage with HLA

Abstract

Forty-eight unrelated patients with idiopathic hemochromatosis were found to have a significantly higher frequency of three HLA antigens (A3, B7 and B14) than 591 healthy controls. A significant association between HLA haplotypes and disease segregations was demonstrated in 14 family studies. A recessive inheritance of a strongly A3-linked disease gene responsible for abnormal iron stores in the heterozygote state is postulated. The lod score value (4.415 for theta = 0.025) is compatible with this hypothesis. However, the excess of HLA-identical pairs of affected sibs does not exclude the possibility of a pseudo-recessiveness due to two codominant genes both HLA-linked. For the first time, a means of screening for high risk subjects is available and therefore offers the possibility of a preventive approach.

Association of HLA-linked hemochromatosis with idiopathic refractory sideroblastic anemia.

“…The proband with sideroblastic anemia had clinically manifest hemochromatosis with skin pigmentation and histologic evidence of early cirrhosis of the liver. Hepatic parenchymal cell stainable iron was grade 4 (normal, 0-1) and the hepatic iron concentration was 602 ,g/100 mg wet liver (normal, 0-29). His brother (II-3) had clinically manifest hemochromatosis with skin pigmentation and histologic evidence of cirrhosis of the liver but not sideroblastic anemia.…”

“…The frequency of HLA-A3 was 72% in patients and 21% in controls, giving a relative risk value of 9.5. Close linkage of the HLA locus to the hemochromatosis locus was demonstrated in pedigree studies (2)(3)(4)(5)(6). We obtained a total lod score in eight pedigrees of +9.8 at a recombination fraction of 0.0 (7).…”

Epidemiologie genetique de l hemochromatose au Saguenay

“…Avec les traitements, l'espérance de vie après le diagnostic est d'environ cinq à dix ans, mais les malades peuvent aussi vivre plus de vingt ans après l'apparition des premiers symptômes (Bothwell, 1979 (Simon et al, 1975). Cette association préférentielle a été confirmée par la suite par d'autres chercheurs dans plusieurs populations (Lipinski et al, 1978;Doran et al, 1981;Edwards et al, 1981) (Llyod et al, 1978;Kuhnl et al, 1978;McCarthy et al, 1979;Edwards et al, 1982;Simon et al, 1987a;Milman et al, 1988 (Lalouel et al, 1985).…”

“…(Borwein et al, 1983 Phémochromatose. Il n'est pas non plus exclu qu'il existe un autre gène responsable de l'hémochromatose plus distant du locus A du système HLA et peut-être même non lié au complexe HLA (Bomford et al, 1977;Lipinski et al, 1978), bien que d'autres admettent qu'il n'existe qu'un seul gène de l'hémochromatose (Lalouel et al, 1985). …”

Mapping recombinant events with molecular markers in hemochromatosis pedigrees

“…1989). Hemochroma tosis is inherited as an autosomal recessive trait (Simon et al, 1977;Cartwright et al, 1978;Lipinski et al, 1978;Kravitz et al. 1979), with a frequency of the homozygous genotype of approximately 5 per 1,000 in Caucasian populations of north ern European extraction (Beaumont et al, 1979;Bassett et al, 1982;Dadone et al, 1982;Borwein et al, 1983;Olsson et al, 1983;Meyer et al, 1987;Edwards et al, 1988).…”