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4. Recipient’s Genetic R702W NOD2 Variant Is Associated with an Increased Risk of Bacterial Infections after Orthotopic Liver Transplantation

Author

Janse, Marcel, primary, de Rooij, Bert-Jan F., additional, van Hoek, Bart, additional, van den Berg, Arie P., additional, Porte, Robert J., additional, Blokzijl, Hans, additional, Coenraad, Minneke J., additional, Hepkema, Bouke G., additional, Schaapherder, Alexander F., additional, Ringers, Jan, additional, Weersma, Rinse K., additional, and Verspaget, Hein W., additional

Published
2013
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5. MMP-2 is a disease-modifying gene in primary sclerosing cholangitis

Author

Sebib Korkmaz, Kerem, primary, de Rooij, Bert-Jan F., additional, van Hoek, Bart, additional, Janse, Marcel, additional, Coenraad, Minneke J., additional, van der Reijden, Johan J., additional, Weersma, Rinse K., additional, Porte, Robert J., additional, Voorneveld, Philip W., additional, Baranski, Andrzej G., additional, and Verspaget, Hein W., additional

Published
2013
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6. Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation

Author

de Rooij, Bert-Jan F., primary, van der Beek, Martha T., additional, van Hoek, Bart, additional, Vossen, Ann C.T.M., additional, Rogier ten Hove, W., additional, Roos, Anja, additional, Schaapherder, Alexander F., additional, Porte, Robert J., additional, van der Reijden, Johan J., additional, Coenraad, Minneke J., additional, Hommes, Daniel W., additional, and Verspaget, Hein W., additional

Published
2011
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7. Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation

Author

de Rooij, Bert-Jan F., primary, van Hoek, Bart, additional, ten Hove, W. Rogier, additional, Roos, Anja, additional, Bouwman, Lee H., additional, Schaapherder, Alexander F., additional, Porte, Robert J., additional, Daha, Mohamed R., additional, van der Reijden, Johan J., additional, Coenraad, Minneke J., additional, Ringers, Jan, additional, Baranski, Andrzej G., additional, Hepkema, Bouke G., additional, Hommes, Daniel W., additional, and Verspaget, Hein W., additional

Published
2010
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8. 337 Donor and Recipient Lectin Complement Pathway Genes Determine the Risk of Clinically Significant Infections After Orthotopic Liver Transplantation

Author

de Rooij, Bert-Jan F., primary, van Hoek, Bart, additional, Ten Hove, Rogier W., additional, Roos, Anja, additional, Bouwman, Lee H., additional, Schaapherder, Alexander F., additional, Porte, Robert J., additional, Daha, Mohamed R., additional, van der Reijden, Johan J., additional, Coenraad, Minneke J., additional, Ringers, Jan, additional, Baranski, Andrzej G., additional, Hepkema, Bouke, additional, Hommes, Daniel W., additional, and Verspaget, Hein W., additional

Published
2010
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10. Recipient’s Genetic R702W NOD2 Variant Is Associated with an Increased Risk of Bacterial Infections after Orthotopic Liver Transplantation.

Author

Janse, Marcel, de Rooij, Bert-Jan F., van Hoek, Bart, van den Berg, Arie P., Porte, Robert J., Blokzijl, Hans, Coenraad, Minneke J., Hepkema, Bouke G., Schaapherder, Alexander F., Ringers, Jan, Weersma, Rinse K., and Verspaget, Hein W.

Subjects
*GENETIC polymorphisms, *BACTERIAL diseases, *LIVER transplantation, *LIVER surgery, *SURGICAL complications, *POSTOPERATIVE period, *INTERNAL medicine
Abstract

Introduction:Orthotopic liver transplantation (OLT) is accompanied by a significant postoperative infection risk. Immunosuppression to prevent rejection increases the susceptibility to infections, mainly by impairing the adaptive immune system. Genetic polymorphisms in the lectin complement pathway of the donor have recently been identified as important risk determinants of clinically significant bacterial infection (CSI) after OLT. Another genetic factor involved in innate immunity is NOD2, which was reported to be associated with increased risk of spontaneous bacterial peritonitis in cirrhotic patients. Methods:We assessed association of three genetic NOD2 variants (R702W, G908R and 3020insC) with increased risk of CSI after OLT. 288 OLT recipient-donor pairs from two tertiary referral centers were genotyped for the three NOD2 variants. The probability of CSI in relation to NOD2 gene variants was determined with cumulative incidence curves and log-rank analysis. Results:The R702W NOD2 variant in the recipient was associated with CSI after OLT. Eight out of 15 (53.3%) individuals with a mutated genotype compared to 80/273 (29.3%) with wild type genotype developed CSI (p=0.027, univariate cox regression), illustrated by a higher frequency of CSI after OLT over time (p=0.0003, log rank analysis). Multivariate analysis (including the donor lectin complement pathway profile) showed independence of this R702W NOD2 association from other risk factors (HR 2.0; p=0.04). The other NOD2 variants, G908R and 3020insC, in the recipient were not associated with CSI. There was no association with CSI after OLT for any of the NOD2 variants in the donor. Conclusion:The mutated NOD2 R702W genotype in the recipient is independently associated with an increased risk of bacterial infections after liver transplantation, indicating a predisposing role for this genetic factor impairing the recipient’s innate immune system. [ABSTRACT FROM AUTHOR]

Published
2013
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