title: Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit.
abstract: Numerous studies associate genetic markers with iron- and erythrocyte-related parameters, but few relate them to iron-clinical phenotypes. Novel SNP rs1375515, located in a subunit of the calcium channel gene CACNA2D3, is associated with a higher risk of anaemia. The aim of this study is to further investigate the association of this SNP with iron-related parameters and iron-clinical phenotypes, and to explore the potential role of calcium channel subunit region in iron regulation. Furthermore, we aim to replicate the association of other SNPs reported previously in our population. We tested 45 SNPs selected via systematic review and fine mapping of CACNA2D3 region, with haematological and biochemical traits in 358 women of reproductive age. Multivariate analyses include back-step logistic regression and decision trees. The results replicate the association of SNPs with iron-related traits, and also confirm the protective effect of both A allele of rs1800562 (HFE) and G allele of rs4895441 (HBS1L-MYB). The risk of developing anaemia is increased in reproductive age women carriers of A allele of rs1868505 (CACNA2D3) and/or T allele of rs13194491 (HIST1H2BJ). Association of SNPs from fine mapping with ferritin and serum iron suggests that calcium channels could be a potential pathway for iron uptake in physiological conditions.
authors.affiliation: Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Baeza-Richer
authors.affiliation: Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arroyo-Pardo
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba (IMIBIC), University of Cordoba, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Blanco-Rojo
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Toxqui
authors.affiliation: Haematology Service, Laboratory and Analyses, Sant Pau Hospital, Barcelona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Remacha
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Madrid, Spain.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Vaquero
authors.affiliation: Department of Toxicology and Health Legislation, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: López-Parra
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics*; D004909:Erythrocyte Indices; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics*; D055815:Young Adult
chemical_list: C531012:CACNA2D3 protein, human; D015220:Calcium Channels; D021122:Protein Subunits; D007501:Iron
keywords: Association study; Calcium channel; Iron deficiency anaemia; Iron uptake; SNPs