Ermini Luca, Weale Michael E, Brown Katherine M, Mesa Irene Rebollo, Howell W Martin, Vaughan Robert, Chowdhury Paramit, Sacks Steven H, Sheerin Neil S
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Department of Medical and Molecular Genetics, King's College, London SE1 9RT, UK.
Immunobiology. 2016 Apr;221(4):528-34. doi: 10.1016/j.imbio.2015.12.006. Epub 2015 Dec 12.
The importance of the innate immune system, including complement, in causing transplant injury and augmenting adaptive immune responses is increasingly recognized. Therefore variability in graft outcome may in part be due to genetic polymorphism in genes encoding proteins of the immune system. This study assessed the relationship between single nucleotide polymorphisms (SNPs) in complement genes and outcome after transplantation. Analysis was performed on two patient cohorts of 650 and 520 transplant recipients. 505 tagged SNPs in 47 genes were typed in both donor and recipient. The relationships between SNPs and graft survival, serum creatinine, delayed graft function and acute rejection were analyzed. One recipient SNP in the gene encoding mannose binding lectin was associated with graft outcome after correction for analysis of multiple SNPs (p=6.41 × 10(-5)). When further correction was applied to account for analysis of the effect of SNPs in both donor and recipient this lost significance. Despite association p values of <0.001 no SNP was significantly associated with clinical phenotypes after Bonferroni correction. In conclusion, the variability seen in transplant outcome in this patient cohort cannot be explained by variation in complement genes. If causal genetic effects exist in these genes, they are too small to be detected by this study.
包括补体在内的固有免疫系统在引发移植损伤和增强适应性免疫反应中的重要性日益得到认可。因此，移植结果的变异性可能部分归因于免疫系统蛋白质编码基因中的遗传多态性。本研究评估了补体基因中的单核苷酸多态性（SNP）与移植后结果之间的关系。对两个分别有650名和520名移植受者的患者队列进行了分析。在供体和受者中对47个基因中的505个标签SNP进行了分型。分析了SNP与移植物存活、血清肌酐、移植肾功能延迟和急性排斥反应之间的关系。在对多个SNP分析进行校正后，编码甘露糖结合凝集素的基因中的一个受者SNP与移植结果相关（p = 6.41×10⁻⁵）。当进一步校正以考虑供体和受者中SNP效应的分析时，这种相关性失去了显著性。尽管关联p值<0.001，但在Bonferroni校正后，没有SNP与临床表型显著相关。总之，该患者队列中观察到的移植结果变异性不能用补体基因的变异来解释。如果这些基因中存在因果遗传效应，它们太小以至于本研究无法检测到。
