No increase in mortality and morbidity among carriers of the C282Y mutation of the hereditary haemochromatosis gene in the oldest old: the Leiden 85-plus study.
BACKGROUND
The C282Y mutation in the gene for haemochromatosis (HFE) has been associated with various diseases at middle age. However, recent studies indicate that penetrance of the C282Y mutation is low. We explored the association between the C282Y mutation, iron metabolism, and morbidity and mortality in participants of the Leiden 85-plus.


METHODS
A cross-sectional comparison and prospective follow-up was conducted in two unselected cohorts of 661 and 552 subjects. All subjects were aged 85 years and over. We determined the prevalence of C282Y homozygous and heterozygous subjects, and the association between the C282Y mutation and iron metabolism, all-cause and specific causes of death.


RESULTS
Prevalence of C282Y homozygosity in both cohorts was 0.2% (1/661 and 1/552, respectively) and of C282Y heterozygosity was 12.4% (82/661) and 11.4% (63/552), respectively. These estimates coincide exactly with reported estimates in younger age groups. Median ferritin level was 97 microg L-1 (IQR 39-162) for heterozygous carriers and 89 microg L-1 (IQR 41-157) for noncarriers (P = 0.66). The serum ferritin concentration for one C282Y homozygous subject, a woman aged 86 years at the time of enrollment in 1986, was 392 microg L-1. Cardiovascular morbidity was comparable between the C282Y heterozygous subjects and the noncarriers in both study cohorts. All-cause and cardiovascular mortality of carriers of the C282Y mutation was similar to that in noncarriers.


CONCLUSIONS
We found two C282Y homozygous subjects, illustrating that homozygosity can be compatible with survival in very old ages. C282Y heterozygosity was not associated with history of cardiovascular disease morbidity, all cause mortality, cardiovascular mortality, or biochemical phenotype of haemochromatosis at old age.
Van Aken
M O
MO
LUMC, Leiden, the Netherlands.
De Craen
A J M
AJ
Gussekloo
J
J
Moghaddam
P Hanifi
PH
Vandenbroucke
J P
JP
Heijmans
B T
BT
Slagboom
P E
PE
Westendorp
R G J
RG
D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000401:mortality; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics* / Q000401:mortality; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009017:Morbidity; D009154:Mutation; D019683:Penetrance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D002097:C-Reactive Protein; D005293:Ferritins