JASN：单一遗传突变或影响肾脏移植的成功率

刊登在国际杂志Journal of the American Society of Nephrology (JASN)上的一项研究揭示，肾脏捐献者其机体细胞的单一遗传突变或可决定器官移植是否成功，这项研究揭示了肾脏捐献者其遗传组成如何影响移植器官的成功比例，为提高器官移植成功率提供了帮助。

一个移植器官接受者必须长期服用免疫抑制药物来抑制新器官植入所带来的机体排斥度，但是许多药物存在严重的副作用，包括引发肾脏损伤。因此抑制肾脏排斥的药物同样会对肾脏有毒性。文章中，研究者揭示了特定的蛋白质如何将药物泵出肾脏细胞，这或许会降低药物对肾脏所带来的毒性。

来自英国伯明翰皇后伊丽莎白医院的研究者试图研究编码蛋白质泵基因的突变是否会影响移植肾脏的健康，他们调查了捐献者和器官接受者基因突变之间的关联。通过研究发现，1）捐献者多重耐药基因MDR1的突变会使得移植器官衰竭风险增加69%；2）对另外3600个捐献者的研究也揭示了此种结果；3）突变会影响MDR1基因编码蛋白的表达，而该蛋白是药物转运蛋白P-糖蛋白；4）在捐献者和接受者机体中并未发现其它和器官存活或衰竭的遗传突变。

不管是对于器官捐献者来说，还是接受者来说，研究基因突变在器官移植领域是一个相对比较新兴的研究，有时候单一的遗传突变或许会影响器官移植的成功率，多重的遗传突变或许在移植器官的长期功能性上扮演着重要角色。

与移植相关的拓展阅读：

• Liver Transpl：美国老年丙肝患者肝移植需求增多
• The Lancet：美国首次成功地开展可呼吸的肺移植
• NAT REV GASTRO HEPAT ：2012年肝癌肝移植研究进展
• JAMA: 体外冲击波辅助治疗可以显著提高经冠脉自体骨髓单个核细胞移植治疗慢性心力衰竭的疗效
• 黄晓军教授获欧洲骨髓移植协会圣安东尼成就奖 更多信息请点击：有关移植更多资讯

Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20–2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21–2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08–3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.