The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) promotes transplant tolerance as well as viral immune escape. HLA-G expression is associated with regulatory elements targeting certain single nucleotide polymorphisms (SNPs) in the HLA-G 3' untranslated region (UTR). Thus, we evaluated the impact of HLA-G 3'UTR polymorphisms as surrogate markers for BK polyomavirus (BKPyV) replication or nephropathy (PyVAN) and acute cellular and antibody mediated rejection (ACR/AMR) in 251 living-donor kidney-transplant recipient pairs. After sequencing of the HLA-G 3'UTR, fourteen SNPs between +2960 and +3227 and the 14 bp insertion/deletion polymorphism, which arrange as UTR haplotypes, were identified. The UTR-4 haplotype in donors and recipients was associated with occurrence of BKPyV/PyVAN compared to the other UTR haplotypes. While the UTR-4 recipient haplotype provided protection against AMR, the UTR-2 donor haplotype was deleteriously associated with ACR/AMR. Deduction of the UTR-2/4 haplotypes to specific SNPs revealed that the +3003C variant (unique for UTR-4) in donors as well as in recipients is responsible for BKPyV/PyVAN and also provides protection against AMR; whereas the +3196G variant (unique for UTR-2) promotes allograft rejection. Thus, HLA-G 3'UTR variants are promising genetic predisposition markers both in donors and recipients that may help to predict susceptibility to either viral infectious complication of BKPyV or allograft rejection.

中文翻译：

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HLA-G 3'非翻译区基因变异是有希望的预后因素，BK多瘤病毒复制和活体供体肾移植后急性排斥反应。

免疫抑制性非经典人类白细胞抗原-G（HLA-G）促进移植耐受性以及病毒免疫逃逸。HLA-G表达与靶向HLA-G 3'非翻译区（UTR）中某些单核苷酸多态性（SNP）的调控元件相关。因此，我们评估了HLA-G 3'UTR多态性作为251个活体供肾肾移植受者中BK多瘤病毒（BKPyV）复制或肾病（PyVAN）以及急性细胞和抗体介导排斥（ACR / AMR）的替代标志物的影响对。对HLA-G 3'UTR进行测序后，鉴定了+2960和+3227之间的14个SNP和14 bp的插入/缺失多态性，它们以UTR单倍型排列。与其他UTR单倍型相比，供体和受体中的UTR-4单倍型与BKPyV / PyVAN的发生有关。虽然UTR-4受体单倍型提供了针对AMR的保护，但UTR-2供体单倍型与ACR / AMR有害相关。将UTR-2 / 4单倍型推导为特定的SNPs表明，供体和受体中的+ 3003C变异体（对UTR-4而言是唯一的）负责BKPyV / PyVAN，并且还提供了针对AMR的保护作用；而+ 3196G变体（适用于UTR-2）促进同种异体移植排斥。因此，HLA-G 3'UTR变体在供体和受体中都是很有前途的遗传易感标记，可帮助预测对BKPyV病毒感染性并发症或同种异体移植排斥的敏感性。将UTR-2 / 4单倍型推导为特定的SNPs表明，供体和受体中的+ 3003C变异体（对UTR-4而言是唯一的）负责BKPyV / PyVAN，并且还提供了针对AMR的保护作用；而+ 3196G变体（适用于UTR-2）促进同种异体移植排斥。因此，HLA-G 3'UTR变异体在捐助者和接受者中都是有前途的遗传易感标记，可帮助预测对BKPyV病毒感染性并发症或同种异体移植排斥的敏感性。将UTR-2 / 4单倍型推导为特定的SNPs表明，供体和受体中的+ 3003C变异体（对于UTR-4而言是唯一的）负责BKPyV / PyVAN，并且还提供针对AMR的保护；而+ 3196G变体（适用于UTR-2）促进同种异体移植排斥。因此，HLA-G 3'UTR变体在供体和受体中都是很有前途的遗传易感标记，可帮助预测对BKPyV病毒感染性并发症或同种异体移植排斥的敏感性。