The previously known strong association with A3 was confirmed (RR = 10.6, P less 10(-9)) and our results indicate clearly that a gene implicated in idiopathic hemochromatosis (IH) determinism is located in the HLA-A region.
In a study of 18 patients with HH (with and without low numbers of CD8+ cells), the level of autophosphorylation of the CD8-associated p56lck as well as its phosphotransferase activity, as determined by phosphorylation of an exogenous substrate, was significantly reduced by two- to three-fold relative to a control population of 23 healthy blood donors (P < 6 x 10(-7).
Because heterozygous carriers of hereditary hemochromatosis (HH) have on the average increased iron stores compared with noncarriers of the HH gene and comprise as much as 15% of the American population, disease risk in HH heterozygotes was investigated.
The DNA of 147 patients of European origin clinically diagnosed with idiopathic hemochromatosis and 193 controls was examined for mutations of the HLA-H gene at nt 845 and nt 187.
In RE cells of GH subjects, we examined the activity of iron regulatory protein (IRP), a reliable indicator of the elusive regulatory labile iron pool, which modulates cellular iron homeostasis through control of ferritin (Ft) and transferrin receptor gene expression.
As a first step in understanding the function of the HLA-H gene product, we generated an antibody to a C-terminal peptide and used it for immunolocalization of the HLA-H protein in the gastrointestinal tract of Finnish and American subjects presumed not to have HH.
In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A.
This report describes the first functional significance of the C282Y mutation by suggesting that an abnormality in protein trafficking and/or cell-surface expression of HLA-H leads to HH disease.
Genotyping of HLA-H, a candidate gene for the diagnosis of hereditary hemochromatosis, was then performed to demonstrate the rapid analysis of biologically relevant samples.