C7 genotype of the donor may predict early bacterial infection after liver transplantation

Abstract

Post-transplantation infection causes high mortality and remains a significant challenge. High clinical risk factors for bacterial infection in recipients are often found in critically ill patients. However, for some recipients, bacterial infections are inevitable. It is conceivable that this susceptibility may be related to the genetics of the donor and recipient. Using expression quantitative trait loci (eQTL) analysis, we found that the C7 rs6876739 CC genotypes and mannan-binding lectin (MBL2) gene polymorphisms of liver donors were significantly associated with bacterial infection in recipients. In an extended validation group of 113 patients, donor C7 rs6876739 genetic variation was an independent risk factor for bacterial infection. The donor C7 rs6876739 CC genotype was associated with lower levels of recipient C7 protein, soluble membrane attack complex (MAC), and IL-1β expression compared with the donor C7 rs6876739 TT genotype. In vitro, the MAC significantly triggered NLRP3 inflammasome activation and IL-1β release, suggesting that the mechanism by which C7 defends against bacteria may involve MAC formation, leading to NLRP3 inflammasome activation and IL-1β release. Our findings may be helpful in identifying transplantation recipients at risk of bacterial infection prior to surgery and may contribute to novel infection prevention strategies and the improvement of postoperative outcomes.

Impact of MBL2 gene polymorphisms on the risk of infection in solid organ transplant recipients: A systematic review and meta-analysis

“…After removing of duplicate studies and detailed evaluation of titles and abstracts, 45 articles were fully assessed for eligibility . Eleven studies (Table ) fulfilled the inclusion and exclusion criteria and were finally included in the present study (PRISMA flow chart shown in Figure ). Two further studies had to be excluded due to the lack of relevant data despite repeated attempts to contact corresponding authors to obtain additional details.…”

“…These 11 studies comprised a total of 1858 SOT recipients: 1494 (80.4%) liver transplant (LT) recipients, 317 (17.1%) kidney or kidney‐pancreas (KT), recipients and 47 (2.5%) lung transplant (LuT) recipients. Although only one study detailed the ethnicity of the genotyped participants, most patients (87.9% [1634/1858]) came from studies performed in countries with predominant Caucasian populations . All but two studies assessed the impact of polymorphisms in both the promoter and exon 1 regions of the MBL2 gene (Table ).…”

“…Although only one study detailed the ethnicity of the genotyped participants, most patients (87.9% [1634/1858]) came from studies performed in countries with predominant Caucasian populations . All but two studies assessed the impact of polymorphisms in both the promoter and exon 1 regions of the MBL2 gene (Table ). Given the instrumental role played by the liver in the synthesis of MBL, donor genotype was investigated in all the studies involving LT, either exclusively or in parallel to the recipient genotype …”

“…All but two studies assessed the impact of polymorphisms in both the promoter and exon 1 regions of the MBL2 gene (Table ). Given the instrumental role played by the liver in the synthesis of MBL, donor genotype was investigated in all the studies involving LT, either exclusively or in parallel to the recipient genotype …”

“…Seven studies (comprising 797 patients) reported separate data on the incidence of posttransplant infection according to genotypic distributions of SNPs located in the promoter/UTR region and/or exon 1 of the MBL2 gene (Table ).…”