Alfaro Rafael, Jaouad El Kaaoui El Band, Llorente Santiago, Jimenez-Coll Victor, Martínez-Banaclocha Helios, Galián José Antonio, Botella Carmen, Moya-Quiles María Rosa, Peña-Moral Jesús de la, Minguela Alfredo, Legaz Isabel, Muro Manuel
Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
Nephrology Service, and University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
OMICS. 2021 Nov;25(11):725-737. doi: 10.1089/omi.2021.0099. Epub 2021 Oct 29.
Kidney transplantation (KT) clinical outcomes are highly variable across patients and would benefit from predictive biomarkers to achieve personalized/precision medicine. The B cell activating factor (BAFF) system signaling plays an essential role in B lymphocytes' homeostasis, and is implicated in activation and survival of B lymphocytes. Single nucleotide polymorphisms (SNPs) in BAFF system genes are therefore strong candidates to identify the genetic mechanisms underpinning variable clinical outcomes in KT. We report here new findings on BAFF system genetic polymorphisms in KT patients in relation to two key phenotypes of clinical interest: graft survival and acute rejection (AR). A total of 168 KT patients, of which 29 suffered AR, participated in this study. The BAFF system polymorphisms in five genes , , , , and were characterized using TaqMan SNP genotyping. Patients with KT who had an AA genotype in polymorphism rs3803800 of the gene had a higher risk of suffering AR ( = 0.046; odds ratios = 3.38, 95% CI: 1.02-11.2). Moreover, patients with AA genotype (rs3803800) in the gene had a significantly lower AR-free time than the GG/GA genotypes (69.2% vs. 85.7%; = 0.037). Of importance, bioinformatics analysis showed that the polymorphism rs3803800 could alter splicing regulation and affect the proliferation-inducing ligand () expression levels. The analysis of graft survival did not show a significant association with the polymorphisms analyzed in this study. In conclusion, the rs3803800 genetic polymorphism from this study of BAFF system genes appears to display importance in AR-free time for KT patients, and thus, warrants further research in independent populations as a putative predictive biomarker of AR. These findings also inform future personalized/precision medicine efforts and functional genomic studies in KT patients.
肾移植（KT）的临床结果在患者之间差异很大，若能有预测性生物标志物来实现个性化/精准医疗，将大有裨益。B细胞活化因子（BAFF）系统信号传导在B淋巴细胞的稳态中起着至关重要的作用，并与B淋巴细胞的激活和存活有关。因此，BAFF系统基因中的单核苷酸多态性（SNP）是确定KT中可变临床结果背后遗传机制的有力候选因素。我们在此报告KT患者中BAFF系统基因多态性与两个关键临床相关表型的新发现：移植物存活和急性排斥反应（AR）。共有168名KT患者参与了本研究，其中29名发生了AR。使用TaqMan SNP基因分型对五个基因（此处原文未列出基因名称）中的BAFF系统多态性进行了表征。在基因（此处原文未列出基因名称）的多态性rs3803800中具有AA基因型的KT患者发生AR的风险更高（P = 0.046；优势比 = 3.38，95%置信区间：1.02 - 11.2）。此外，基因（此处原文未列出基因名称）中具有AA基因型（rs3803800）的患者无AR时间明显短于GG/GA基因型患者（69.2%对85.7%；P = 0.037）。重要的是，生物信息学分析表明，多态性rs3803800可改变剪接调控并影响增殖诱导配体（此处原文未列出配体名称）的表达水平。移植物存活分析未显示与本研究中分析的多态性有显著关联。总之，本研究中BAFF系统基因的rs3803800基因多态性似乎在KT患者的无AR时间方面具有重要意义，因此，作为AR的一种假定预测生物标志物，值得在独立人群中进一步研究。这些发现也为未来KT患者的个性化/精准医疗努力和功能基因组学研究提供了参考。
