Haemochromatosis-associated HFE genotypes in English blood donors: age-related frequency and biochemical expression.
OBJECTIVE
There are limited data on the frequency and biochemical expression of the haemochromatosis-associated mutations C282Y and H63D in healthy people.


METHODS
We genotyped (bi-directional PCR amplification of specific alleles method) and performed serum iron studies in randomly selected English male blood donors (<4 previous units donated) in four age bands <30, 30-40, 40-50 and >50 years.


RESULTS
In 6261 subjects, frequency of C282Y homozygosity (+/+) was 0.3%, C282Y/H63D compound heterozygosity (+/-) 2.0%, and H63D and C282Y heterozygosity +/-, 21.7 and 10.4%, respectively. Genotype distribution was within Hardy-Weinberg equilibrium in each age band. C282Y +/- frequency fell from 11.7% in subjects <30 years to 8.2% in subjects >50 (Chi2 7.19; P<0.005). No such trend was seen for C282Y +/+. In C282Y +/+ subjects, median serum ferritin was 247 (range 60-2449) microg/l and exceeded >500 microg/l in only two of 18 subjects. Compared to wild/wild (-/-) subjects, C282Y and H63D +/- subjects had slightly higher serum iron and lower unsaturated iron binding concentrations, similar overall serum ferritin values but higher serum ferritin values in subjects who had previously donated blood.


CONCLUSIONS
C282Y +/+ shows limited biochemical expression and no trend towards age-related attrition. C282Y and H63D +/- may protect against iron deficiency.
Chambers
Vanessa
V
Academic Unit of Child Health, University of Sheffield, Sheffield, UK.
Sutherland
Lindsey
L
Palmer
Karren
K
Dalton
Ann
A
Rigby
Alan S
AS
Sokol
Robert
R
Pollitt
Rodney
R
Tanner
Stuart
S
Gleeson
Dermot
D
D000328:Adult; D017677:Age Distribution; D001782:Blood Donors / Q000706:statistics & numerical data*; D004739:England / Q000453:epidemiology; D005293:Ferritins / Q000097:blood; D005838:Genotype; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron