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Disease Markers
Volume 34 (2013), Issue 2, Pages 121-129

Identification of a Novel Quantitative Trait Nucleotype Related to Iron Status in a Calcium Channel Gene

Carlos Baeza-Richer,1 Ruth Blanco-Rojo,2 Ana M. López-Parra,1 Anna Brichs,3 Stefania Bertoncini,4 Ana M. Pérez-Granados,2 Alfonso Buil,3 José M. Soria,3 Eduardo Arroyo-Pardo,1 and M. Pilar Vaquero2

1Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
2Department of Metabolism and Nutrition, Institute of Food Science, Food Technology and Nutrition, Spanish National Research Council, Madrid, Spain
3Unit of Genomic of Complex Diseases, Institute of Biomedical Research, Barcelona, Spain
4Department of Biology, University of Pisa, Pisa, Italy

Received 24 December 2012; Accepted 24 December 2012

Copyright © 2013 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Several iron-related parameters have been reported to show significant heritability, and thus, seemed to be genetically regulated. A genome wide family-based study revealed two regions that showed a linkage signal with transferrin receptor levels. The aim of the study was to identify genetic markers associated with iron status biomarkers. Ten SNPs selected from the literature were tested, and parameters related to iron metabolism were analysed, in a group (n=284) of Spanish women. Data were analyzed using Bayesian Model Averaging (BMA) test and decision trees. The rs1375515, located in an intronic region of the calcium channel gene CACNA2D3, showed strong associations with levels of mean corpuscular volume according to BMA test, and with levels of haemoglobin and ferritin according to decision trees. The allele G was associated to low levels of these parameters which suggests higher iron deficiency anaemia risk. This SNP along with the C282Y mutation explained significant differences in the distribution of individuals in three iron-related clinical phenotypes (normal, iron deficient and iron deficiency anaemic). In conclusion, the rs1375515, or other genetic polymorphisms in linkage, may play important roles in iron status, probably by affecting the function of a calcium channel. These findings may be useful for further investigation in the etiology of iron diseases.