title: Variant rs1801157 in the 3'UTR of SDF-1ß does not explain variability of healthy-donor G-CSF responsiveness.
abstract: The genetics responsible for the inter-individually variable G-CSF responsiveness remain elusive. A single nucleotide polymorphism (SNP) in the 3'UTR of CXCL12, rs1801157, was implicated in X4-tropic HiV susceptibility and later, in two small studies, in G-CSR responsiveness in patients and donors. The position of the SNP in the 3'UTR together with in-silico predictions suggested differential binding of micro-RNA941 as an underlying mechanism. In a cohort of 515 healthy stem cell donors we attempted to reproduce the correlation of the CXCL12 3'UTR SNP and mobilization responses and tested the role of miR941 in this context. The SNP was distributed with the expected frequency. Mobilization efficiency for CD34+ cells in WT, heterozygous and homozygous SNP individuals was indistinguishable, even after controlling for gender. miR941 expression in non-hematopoietic bone marrow cells was undetectable and miR941 did not interact with the 3' UTR of CXCL12. Proposed effects of the SNP rs1801157 on G-CSF responsiveness cannot be confirmed in a larger cohort.
authors: German Red Cross Blood Service Baden-Württemberg-Hesse, Frankfurt, Germany.
authors: Miriam
authors: M
authors: Schulz
authors: Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors: Darja
authors: D
authors: Karpova
authors: Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors: Gabriele
authors: G
authors: Spohn
authors: Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors: Annette
authors: A
authors: Damert
authors: German Red Cross Blood Service Baden-Württemberg-Hesse, Frankfurt, Germany; Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany.
authors: Erhard
authors: E
authors: Seifried
authors: Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany.
authors: Vera
authors: V
authors: Binder
authors: German Red Cross Blood Service Baden-Württemberg-Hesse, Frankfurt, Germany; Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany; University of Washington, Department of Medicine, Division of Hematology, Seattle, WA, United States of America.
authors: Halvard
authors: H
authors: Bönig
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D057809:HEK293 Cells; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D035683:MicroRNAs / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D033581:Stem Cell Transplantation
chemical_list: D020413:3' Untranslated Regions; D054377:Chemokine CXCL12; C581560:MIRN941 microRNA, human; D035683:MicroRNAs; D016179:Granulocyte Colony-Stimulating Factor