The HLA‐A1‐B8 haplotype hitchhiking with the hemochromatosis mutation: does it affect the phenotype?

Abstract

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.

Common local founder effects for Wilson's disease and hereditary hemochromatosis; mutation studies of a large family

“…This territorial happened to be populated by settlers carrying C282Y mutations whose origin and HLA haplotypes have been previously described [19,26]. Some of the HH patients (18.5%) were identified in Göteborg far away from their birthplaces.…”

“…Whether Wilson mutations might have affected the phenotype of hemochromatosis subjects is not known. A severely affected HH family was accounted for by another genetic defect, congenital spherocytosis, known to affect the phenotype [26,32].…”

“…Previous studies have shown that WND is rare in Sweden as compared with other countries [26]. Based on the number of patients known in 2000 (n = 36), the prevalence was estimated to be 1/250,000-300,000 including 6 patients (16.6%) from the study area.…”

“…It appeared that the risk to capture a hemochromatosis mutation was most often associated with a migration out of the birth parish (A) into settlements of the northwest. Settlers in those areas carried C282Y mutations whose origin and HLA haplotypes have been previously described [19,26]. Twenty-three of 26 HH families (88.5%) had such background as compared with 11.5% (p < 0.05) of those who stayed in their birth parish.…”

“…One HH family (arrow) had a particularly serious phenotype with two brothers dying from advanced disease (bronze diabetes). This was, however, most probably caused by coinheritance of another mutation causing congenital spherocytosis present in their mother and their grandfather [26].…”