Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study.
OBJECTIVE
In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH.


METHODS
Data on HFE-genotype, iron parameters, demographics, lifestyle factors and health, were collected from 224 Dutch C282Y homozygous patients with clinically diagnosed HH and 735 of their first-degree family members (FDFM), all participating in the HEmochromatosis FAmily Study (HEFAS).


RESULTS
The best predictive multivariable model forecasted 45% of variation of the serum ferritin levels. In this model severity of iron overload in the proband significantly predicted serum ferritin levels in FDFM. Other significant determinants in this model consisted of C282Y homozygosity, compound heterozygosity, age at testing for serum ferritin and supplemental iron intake, whereas a low body mass index showed a protective effect.


CONCLUSIONS
This study provides a model to assess the risk of development of iron overload for relatives of probands with HH. These results might be instrumental in the development of an optimal strategy for future family screening programs.
Jacobs
Esther M G
EM
Department of Clinical Chemistry 441, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Hendriks
Jan C M
JC
van Deursen
Cees Th B M
CT
Kreeftenberg
Herman G
HG
de Vries
Richard A
RA
Marx
Joannes J M
JJ
Stalenhoef
Anton F H
AF
Verbeek
André L M
AL
Swinkels
Dorine W
DW
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D005293:Ferritins / Q000097:blood*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000097:blood* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D009426:Netherlands; D012307:Risk Factors; D012720:Severity of Illness Index
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins