title: Genomewide linkage analysis of soluble transferrin receptor plasma levels.
abstract: Genetic control of soluble transferrin receptor (sTfR) levels was demonstrated using family-based studies (GAIT, Genetic Analysis of Idiopathic Thrombophilia project); moreover, a genetic relationship was observed between sTfR and the risk for thrombosis, suggesting that these phenotypes shared genetic determinants. We studied the regions that control sTfR. To assess such regions, a full genome scan was carried out using 604 highly polymorphic deoxyribonucleic acid markers (resolution 7.3 cM) in 21 extended pedigrees (358 individuals). Then, a quantitative trait linkage analysis was performed using variance components methods. The genomewide scan linkage analysis showed two regions (quantitative trait locus or QTL) with significant limit of detection (LOD) scores (2q23.14, LOD score = 2.64, nominal p = 0.00024; 3q21.2, LOD score = 1.94, nominal p = 0.0014). There were no obvious candidate genes in these regions. In conclusion, this linkage analysis suggested the existence of a QTL in 2q23.14 that probably harbored a gene (or genes) controlling sTfR levels. Moreover, a second linkage signal was observed in 3q21.2; albeit the evidence for this second locus was lower. The next step will be to identify the gene(s) and its possible involvement in thrombosis and iron homeostasis.
authors.affiliation: Hematology Department, Hospital de Sant Pau, Avda Padre Claret 167, Barcelona, 08025, Spain. aremacha@hsp.santpau.es
authors.forename: Angel F
authors.initials: AF
authors.lastname: Remacha
authors.forename: Joan C
authors.initials: JC
authors.lastname: Souto
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Soria
authors.forename: Alfonso
authors.initials: A
authors.lastname: Buil
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Sardà
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Jordi
authors.initials: J
authors.lastname: Fontcuberta
mesh_terms: D002874:Chromosome Mapping / Q000379:methods; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D011990:Receptors, Transferrin / Q000097:blood / Q000235:genetics*; D019851:Thrombophilia / Q000097:blood / Q000235:genetics*; D013927:Thrombosis / Q000097:blood / Q000235:genetics
chemical_list: D005819:Genetic Markers; D011990:Receptors, Transferrin