Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization
| Autor: | Jean-Pierre Cartron, Carole Saison, Hein Hustinx, Thierry Peyrard, Bryan A. Ballif, Edmond Lee, Virginie Helias, Lucienne Mannessier, Shane Grimsley, Lionel Arnaud, Geoff Daniels |
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| Rok vydání: | 2015 |
| Předmět: |
Nonsynonymous substitution
Male Candidate gene medicine.medical_specialty Immunology Nucleoside transporter Equilibrative nucleoside transporter 1 Biochemistry Polymorphism Single Nucleotide Protein Structure Secondary White People Equilibrative Nucleoside Transporter 1 Ectopic calcification Mice medicine Animals Humans Blood type Mice Knockout biology Transfusion Medicine Ossification Heterotopic Cell Biology Hematology medicine.disease Molecular biology Null allele Surgery biology.protein Blood Group Antigens Female Nucleoside |
| Zdroj: | Blood. 125(23) |
| ISSN: | 1528-0020 |
| Popis: | The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible for the At(a-) blood type. The resulting p.Glu391Lys variation in the last extracellular loop of the equilibrative nucleoside transporter 1 (ENT1; also called SLC29a1) is known not to alter its ability to transport nucleosides and nucleoside analog drugs. Furthermore, we identified 3 individuals of European ancestry who are homozygous for a null mutation in SLC29A1 (c.589+1GC) and thus have the Augustine-null blood type. These individuals lacking ENT1 exhibit periarticular and ectopic mineralization, which confirms an important role for ENT1/SLC29A1 in human bone homeostasis as recently suggested by the skeletal phenotype of aging Slc29a1(-/-) mice. Our results establish Augustine as a new blood group system and place SLC29A1 as a new candidate gene for idiopathic disorders characterized with ectopic calcification/mineralization. |
| Databáze: | OpenAIRE |
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