Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization
Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization
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DOI：
10.1182/blood-2015-03-631598
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发表时间：
2015-06-04
期刊：
影响因子：
20.3
通讯作者：
Arnaud, Lionel
中科院分区：
文献类型：
--
作者：
Daniels, Geoff;Ballif, Bryan A.;Arnaud, Lionel
奥古斯丁阴性的别名At（a-）血型，似乎仅限于非洲血统的人，在半个世纪前被发现，但仍然是最后一种没有已知遗传基础的血型之一。在这里，我们报告说，在SLC 29 A1（rs 45458701）的非同义单核苷酸多态性是负责在（a-）血型。已知平衡型核苷转运蛋白1（ENT 1;也称为SLC 29 a1）的最后一个细胞外环中产生的p.Glu391Lys变异不会改变其转运核苷和核苷类似物药物的能力。此外，我们鉴定了3名欧洲血统的个体，他们是SLC 29 A1无效突变的纯合型（c.58911G>C），因此具有奥古斯丁无效血型。这些缺乏ENT 1的个体表现出关节周围和异位矿化，这证实了ENT 1/SLC 29 A1在人骨稳态中的重要作用，正如最近由衰老的Slc 29 a1（-/-）小鼠的骨骼表型所表明的那样。我们的研究结果建立奥古斯丁作为一个新的血型系统和地方SLC 29 A1作为一个新的候选基因的特发性疾病的特点是异位钙化/矿化。
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.