ABCC10基因变异,小说替诺福韦,与肾小管功能障碍有关。

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Pushpakom SP、Liptrott新泽西Rodriguez-Novoa年代,Labarga P, V索里亚诺,Albalater M, Hopper-Borge E, Bonora年代,Di Perri G, DJ,邱年代,Pirmohamed M,欧文

ABCC10基因变异,小说替诺福韦,与肾小管功能障碍有关。

J感染说。2011年7月1日,204(1):145 - 53年。doi: 10.1093 / infdis / jir215。

PubMed ID

21628669 (在PubMed

]

文摘

背景:泰诺福韦(TFV)导致肾小管功能障碍(KTD)在某些病人,但机制了解甚少。基因变异在TFV运输车牵连;我们探索ABCC10传输是否TFV以及是否ABCC10单核苷酸多态性(snp)与KTD相关联。方法:TFV积累在父母和评估ABCC10-transfected HEK293细胞(HEK293-ABCC10), CD4(+)细胞和monocyte-derived巨噬细胞(mdm)。证实了底物特异性cepharanthine (ABCC10抑制剂)和小干扰RNA (siRNA)研究。在ABCC10十四个snp基因分型人类免疫缺陷病毒呈阳性的患者身上KTD (n = 19)或没有KTD(控制;n = 96)。单核苷酸多态性和单体型分析是使用Haploview执行。结果:TFV积累显著低于HEK293-ABCC10细胞系比父母HEK293细胞(低35%;P = .02点); this was reversed by cepharanthine. siRNA knockdown of ABCC10 resulted in increased accumulation of TFV in CD4(+) cells (18%; P = .04) and MDMs (25%; P = .04). Two ABCC10 SNPs (rs9349256: odds ratio [OR], 2.3; P = .02; rs2125739, OR, 2.0; P = .05) and their haplotype (OR, 2.1; P = .05) were significantly associated with KTD. rs9349256 was associated with urine phosphorus wasting (P = .02) and beta2 microglobulinuria (P = .04). CONCLUSIONS: TFV is a substrate for ABCC10, and genetic variability within the ABCC10 gene may influence TFV renal tubular transport and contribute to the development of KTD. These results need to be replicated in other cohorts.

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药物转运蛋白

药物	转运体	类	生物	药理作用	行动
替诺福韦disoproxil	耐多药resistance-associated蛋白7	蛋白质	人类	未知的	底物	细节