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Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

Ruth Blanco-Rojo1, Carlos Baeza-Richer2, Ana M López-Parra2, Ana M Pérez-Granados1, Anna Brichs3, Stefania Bertoncini24, Alfonso Buil3, Eduardo Arroyo-Pardo2, Jose M Soria3 and M Pilar Vaquero1*

Author Affiliations

1 Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Madrid, Spain

2 Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University of Madrid, Spain

3 Unit of Genomic of Complex Diseases, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain

4 Department of Biology, University of Pisa, Pisa, Italy

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Nutrition & Metabolism 2011, 8:69  doi:10.1186/1743-7075-8-69

Published: 6 October 2011



Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs) known to be related to iron metabolism were studied in menstruating women.


A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA) test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141) was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression.


Four variants, two in the transferrin gene (rs3811647, rs1799852) and two in the HFE gene (C282Y, H63D), explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found.


In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.

Transferrin gene; HFE gene; serum transferrin; transferrin saturation; iron deficiency anaemia; SNP; menstruating women; iron intake; association study; genetic markers