The relationship between donor-recipient genetic distance and long-term kidney transplant outcome.
The relationship between donor-recipient genetic distance and long-term kidney transplant outcome.
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DOI：
10.12688/hrbopenres.13021.1
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发表时间：
2020
影响因子：
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通讯作者：
Cavalleri GL
中科院分区：
文献类型：
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作者：
Stapleton CP;Lord GM;UK and Ireland Renal Transplant Consortium;Conlon PJ;Cavalleri GL
工作背景：我们开始量化无关的肾脏供体-受体对之间的共同遗传祖先，并将其作为移植失败时间的预测因子进行测试。 研究方法：在一个同质的，无关的，欧洲队列的死亡供体肾移植对（n对= 1，808），我们计算，使用共同的遗传变异，在基因（n位点= 40，053）和基因组水平上的共同祖先。我们对跨膜蛋白编码基因（n转录本= 8，637）进行了亚分析，并尝试复制先前发表的非同义跨膜错配评分。在生存模型中针对死亡时间审查的移植失败测试了共同遗传祖先的测量值。 结果如下：在人类白细胞抗原（HLA）中计算的共同祖先与具有高血清学不匹配（n对= 186）的个体中的移植物存活显著相关，这些个体与没有任何HLA不匹配的个体，表明共同祖先计算的特定基因座可以捕获与影响移植物结果的基因的已知关联。在基因水平、全基因组范围、跨膜亚群或非同义跨膜错配评分分析中，没有其他共同祖先的指标是移植失败时间的显著预测因子。 结论：在一个大的无关的，死亡的供体欧洲血统的肾移植队列中，共同的供体-受体遗传血统，使用共同的遗传变异计算，在预测移植结果的基因组规模和基因水平（在HLA位点以外）的价值有限。
Background: We set out to quantify shared genetic ancestry between unrelated kidney donor-recipient pairs and test it as a predictor of time to graft failure. Methods: In a homogenous, unrelated, European cohort of deceased-donor kidney transplant pairs (n pairs = 1,808), we calculated, using common genetic variation, shared ancestry at the genic (n loci=40,053) and genomic level. We conducted a sub-analysis focused on transmembrane protein coding genes (n transcripts=8,637) and attempted replication of a previously published nonsynonymous transmembrane mismatch score. Measures of shared genetic ancestry were tested in a survival model against time to death-censored graft failure. Results: Shared ancestry calculated across the human leukocyte antigen (HLA) significantly associated with graft survival in individuals who had a high serological mismatch (n pairs = 186) with those who did not have any HLA mismatches indicating that shared ancestry calculated specific loci can capture known associations with genes impacting graft outcome. None of the other measures of shared ancestry at a genic level, genome-wide scale, transmembrane subset or nonsynonymous transmembrane mismatch score analysis were significant predictors of time to graft failure. Conclusions: In a large unrelated, deceased-donor European ancestry renal transplant cohort, shared donor-recipient genetic ancestry, calculated using common genetic variation, has limited value in predicting transplant outcome both on a genomic scale and at a genic level (other than at the HLA loci).