title: Identification of a novel quantitative trait nucleotype related to iron status in a calcium channel gene.
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.
authors: Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain. cbaezaricher@med.ucm.es
authors: Carlos
authors: C
authors: Baeza-Richer
authors: Ruth
authors: R
authors: Blanco-Rojo
authors: Ana M
authors: AM
authors: López-Parra
authors: Anna
authors: A
authors: Brichs
authors: Stefania
authors: S
authors: Bertoncini
authors: Ana M
authors: AM
authors: Pérez-Granados
authors: Alfonso
authors: A
authors: Buil
authors: José M
authors: JM
authors: Soria
authors: Eduardo
authors: E
authors: Arroyo-Pardo
authors: M Pilar
authors: MP
authors: Vaquero
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000235:genetics*; D001499:Bayes Theorem; D015220:Calcium Channels / Q000235:genetics*; D004909:Erythrocyte Indices / Q000235:genetics; D005260:Female; D005293:Ferritins / Q000235:genetics; D005787:Gene Frequency; D060148:HapMap Project; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D055815:Young Adult
chemical_list: C531012:CACNA2D3 protein, human; D015220:Calcium Channels; D005293:Ferritins; D007501:Iron