Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization

作者：Daniels Geoff; Ballif Bryan A; Helias Virginie; Saison Carole; Grimsley Shane; Mannessier Lucienne; Hustinx Hein; Lee Edmond; Cartron Jean Pierre; Peyrard Thierry; Arnaud Lionel^*

来源：Blood, 2015, 125(23): 3651-3654.

DOI：10.1182/blood-2015-03-631598

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.58911G>C) 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.

• 出版日期2015-6-4