RT Journal Article
SR Electronic
T1 The significance of haemochromatosis gene mutations in the general population: implications for screening
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 830
OP 836
DO 10.1136/gut.43.6.830
VO 43
IS 6
A1 M J Burt
A1 P M George
A1 J D Upton
A1 J A Collett
A1 C M A Frampton
A1 T M Chapman
A1 T A Walmsley
A1 B A Chapman
YR 1998
UL http://gut.bmj.com/content/43/6/830.abstract
AB Background—Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown. Aims—To determine the frequency ofHFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis. Methods—Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis. Results—Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone. Conclusions—HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis.