Phenotypic expression of the HLA linked iron-loading gene in males over the age of 40 years: a population study using serial serum ferritin estimations.

The frequency of the HLA linked iron-loading gene was assessed in 1783 Afrikaner men over the age of 40 years living in the South Western Cape. Measurements, made on three occasions over a 4.5 year period, included the serum ferritin concentration, a screening test for reduced unsaturated iron-binding capacity and the percentage transferrin saturation. The serum gamma-glutamyl transferase concentration was used as a marker of alcohol abuse. The diagnosis of homozygosity was based on a serum ferritin concentration that was persistently greater than 400 micrograms l-1 and a percentage transferrin saturation greater than 55%. Using these criteria, 17 subjects were diagnosed as homozygous, corresponding to a disease frequency of 0.0095, a gene frequency of 0.0976 and a heterozygote frequency of 0.176 (95% confidence limits: 0.135-0.213). None of the subjects had overt clinical haemochromatosis. Typing for the HLA-A, -B, -C and -DR loci showed that the HLA-A3 allele (frequency 0.6471 and relative risk 4.4) was the only independent marker for the iron-loading gene in this asymptomatic population. Using the present approach it was not possible to distinguish between heterozygotes, alcohol abusers and normal subjects with serum ferritin concentrations at the upper end of the normal range.