A non-interventional study of the genetic polymorphisms of NOD2 associated with increased mortality in non-alcoholic liver transplant patients

Background: Infections after liver transplantationarethemaincauseofdeathinthefirstyear.Recentreportsindicatethat NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease inbone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liverrecipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, theincidence of infections and patient survival.

Methods: During a period of 20-months, 231 patients were recruited in this non-interventional, prospective study.Thirteen different SNPs and their impact on the patients’survival, infection rate, and use of dialysis were assessed.

Results: NOD 2 wildtype genes were protective with respect to the survival of non-alcoholic, cirrhotic transplant patients(3 year survival: 66.8% wildtype vs. 42.6% gene mutation, p = 0.026). This effect was not observed in alcoholic transplantrecipients.The incidence of dialysis-dependent kidney failure and infectioninthelivertransplantpatients was not influenced byNOD 2 gene polymorphisms. No effect was noted in the remaining 12 SNPs.Patients with early allograft dysfunction experienced significantly more infections, required dialysis and had significantlyworse survival.In contrast, the donor-risk-index had no impact on the infection rate, use of dialysis or survival.

Conclusion: NOD2 gene variants seem to play a key role in non-alcoholic, liver transplant recipients. However these datashould be validated in a larger cohort.



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