Heritability of serum iron, ferritin and transferrin saturation in a genetically isolated population, the Erasmus Rucphen Family (ERF) Study.
BACKGROUND
Iron has been implicated in the pathogenesis of various disorders. Mutations in the HFE gene are associated with an increase in serum iron parameters. The aim of this study was to estimate the heritability in serum iron parameters explained by HFE.


METHODS
Ninety families (980 subjects) were included in the present analysis. Heritability estimation was conducted using the variance component method. The likelihood ratio test was used to compare models. Phenotypic and genetic correlations between serum iron parameters were calculated.


RESULTS
The heritability (h(2) +/- SE) estimates were 0.23 +/- 0.07 (p < 0.0001) for iron, 0.29 +/- 0.09 (p < 0.0001) for ferritin and 0.28 +/- 0.07 (p < 0.0001) for transferrin saturation while adjusting for age, age(2) and sex. The HFE genotypes explained between 2 to 6% of the sex and age-adjusted variance in serum iron, ferritin and transferrin saturation. There was a high genetic correlation between serum iron parameters, suggesting pleiotropy between these traits.


CONCLUSIONS
A substantial proportion of the variance of iron, ferritin and transferrin saturation can be explained by additive genetic effects, independent of sex and age. The HFE genotypes explained a considerable proportion of serum iron parameters and may be an important factor in the complex iron network.
Njajou
O T
OT
Genetic Epidemiology Unit, Departments of Epidemiology & Biostatistics and Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands. o.njajou@erasmusmc.nl
Alizadeh
B Z
BZ
Aulchenko
Y
Y
Zillikens
M C
MC
Pols
H A P
HA
Oostra
B A
BA
Swinkels
D W
DW
van Duijn
C M
CM
D005260:Female; D005293:Ferritins / Q000097:blood*; D005838:Genotype; 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; D019655:Quantitative Trait, Heritable; D014168:Transferrin / Q000378:metabolism*
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron