NOD2 variant linked to liver, intestinal failure in short-gut syndrome
MedWire News: Investigators report that a variant in the nucleotide-binding oligomerization protein 2 gene (NOD2), previously associated with Crohn's disease (CD), is linked with combined liver and intestinal failure in patients with short-gut syndrome.
"The NOD2 gene single nucleotide polymorphisms (SNPs) associated with CD were recently associated with severe rejection after small bowel transplantation (SBT)," say Rakesh Sindhi (University of Pittsburgh, Pennsylvania, USA) and colleagues.
They carried out a study of 85 children (60 Caucasian, 18 African-American, six Hispanic, and one of other ethnicity) requiring isolated SBT or combined liver and small bowel transplantation (LSBT) to assess whether deficient innate immunity due to NOD2 SNP genotype - rs2066845, rs2066847, and rs2066844 - results in intestine failure requiring SBT or LSBT.
To minimize confounding due to ethnic variability in allele frequencies, only the 60 Caucasian children were included in the analysis. A cohort of 39 Caucasian children and adults who underwent small bowel transplantation were also genotyped for replication purposes.
The team found that the minor allele frequencies of the NOD2 SNPs rs2066845 and rs2066847 did not vary significantly between patients in the SBT/LSBT cohort and a group of 538 healthy Caucasians from North America (controls).
The minor allele frequency for rs2066844 was significantly higher in patients who had LSBT (n=37), at 13.5%, than in healthy controls, at 3.6%. This association was successfully repeated in the replication cohort.
SBT patients (n=23) did not have a significantly greater minor allele frequency for rs2066844 than controls in either cohort, however, at 2.2%.
The researchers note that among LSBT patients who had the same immunosuppressant regime, presence of the minor allele of rs2066844 was significantly associated with early rejection, decreased survival, and a 20 times greater risk for septic death than absence of the minor allele.
But more severe steroid-resistant rejection and graft loss were not linked with NOD2 genotype.
"Replication of our findings in additional independent cohorts may encourage more aggressive measures to manage intestinal failure when NOD2 risk alleles are present and to avoid progression to liver failure," conclude the team in the American Journal of Gastroenterology.
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By Helen Albert