Affiliations: Department of Toxicology and Health Legislation,
Faculty of Medicine, Complutense University of Madrid, Madrid, Spain | Department of Metabolism and Nutrition, Institute of
Food Science, Food Technology and Nutrition, Spanish National Research Council,
Madrid, Spain | Unit of Genomic of Complex Diseases, Institute of
Biomedical Research, Barcelona, Spain | Department of Biology, University of Pisa, Pisa,
Italy
Note: [] Corresponding author: Carlos Baeza-Richer, Department of
Toxicology and Health Legislation, Faculty of Medicine, Complutense University
of Madrid, Complutense Avenue, 28040 Madrid, Spain. Tel./Fax: +34 913 941 576;
E-mail: cbaezaricher@med.ucm.es
Abstract: 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.
Keywords: Quantitive trait nucleotype, iron deficiency anaemia, calcium channel gene, SNP, association study
