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

Abstract

BackgroundInfections after liver transplantation are the main cause of death in the first year. Recent reports indicate that NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease in bone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13 single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liver recipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, the incidence of infections and patient survival.MethodsDuring 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.ResultsNOD 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 transplant recipients.The incidence of dialysis-dependent kidney failure and infection in the liver transplant patients was not influenced by NOD 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 significantly worse survival.In contrast, the donor-risk-index had no impact on the infection rate, use of dialysis or survival.ConclusionNOD2 gene variants seem to play a key role in non-alcoholic, liver transplant recipients. However these data should be validated in a larger cohort.

Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

“…We recorded a 27.9% acute rejection rate associated with the CT genotype compared with 12.5% in relation to the TT genotype at rs2066844. These results are in agreement with those obtained from other studies, including our own, where polymorphisms in this gene influence the organ survival outcomes of transplant patients [ 20 , 47 , 48 ]. Due to the potential relevance of this finding, we think that this gene should be included in future studies including more patients.…”

The Gut Microbiota and Liver Disease

“…Genetic polymorphisms of NOD2 are associated with increased mortality in nonalcoholic liver transplant patients 44 . Inflammasomes recognize pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) that cleavage proinflammatory cytokines such as pro-interleukin (IL)-1β 44 and pro-IL-18.…”

“… 42 , 43 Genetic polymorphisms of NOD2 are associated with increased mortality in nonalcoholic liver transplant patients. 44 Inflammasomes recognize pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) that cleavage proinflammatory cytokines such as pro-interleukin (IL)-1β 44 and pro-IL-18. Mice deficient for nucleotide-binding domain and leucine-rich repeat-containing protein 6 (NLRP-6), and hence less intestinal IL-18, showed altered fecal microbiota characterized by an increase of the bacterial phyla Bacteroidetes (Prevotellaceae) and TM7.…”

Intestinal Fibrosis and Liver Fibrosis: Consequences of Chronic Inflammation or Independent Pathophysiology?

“…In addition, essentially all animal models of intestinal fibrosis appear to be dependent on the presence of a microflora to initiate or perpetuate gut inflammation and fibrosis [25]. Although direct evidence about the innate immunity gene variants in liver fibrosis is lacking, several studies have shown that NOD2 is associated with the increased mortality in nonalcoholic liver transplant patients [30] or the increased risk of spontaneous bacterial peritonitis in patients with liver cirrhosis [31,32]. …”