title: 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.
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: Baojie
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: PuSen
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: ChunGuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, 85 Wu Jing Road, 200080, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000328:Adult; D000483:Alleles; D019540:Area Under Curve; D001424:Bacterial Infections / Q000209:etiology*; D015331:Cohort Studies; D003184:Complement C7 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D017093:Liver Failure / Q000628:therapy; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012372:ROC Curve; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D003184:Complement C7; D053583:Interleukin-1beta; D037601:Mannose-Binding Lectin; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein