954 Carbohydrate Digestion in Congenital Sucrase Isomaltase Deficient and Recurrent Abdominal Pain Children Assesed by 13C- Starch Breath Test

Abstract

BACKGROUND: Intestinal allograft rejection is a severe complication in small bowel transplantation. Identifying involved pathogenetic mechanisms might make it possible to predict or even prevent rejection and intestinal graft failure. Rejection resembles Crohn's disease (CD) clinically and histopathologically. We investigated the role of CD-associated genetic loci, including NOD2 variants in rejection and graftfailure. METHODS: 99 recipients and 71 donors from the University of Nebraska Medical Center, USA were genotyped for three NOD2 variants and single nucleotide polymorphisms in IBD5, ATG16L1, IRGM, MST1, IL23R, STAT3 and JAK2. Genotypes were related to clinical outcomes rejection, graftfailure and patient-survival using Kaplan-Meier curves and log-rank analysis. RESULTS: Only the MST1 riskallele was more frequent in recipients compared to donors (30,8% and 20,4%, p=0,032). For the other loci, including NOD2, allelic distribution was equal within the two groups. No single locus was significantly associated with rejection, graftfailure or patientsurvival. There is no significant difference in clinical endpoints whether the recipient has a low or high number of risk alleles. Individuals receiving a donorgraft with ≤5 riskalleles in total, have decreased rejection-free survival compared to ≥6 riskalleles (p=0,040), but increased patient three-year survival (mortality: 4/19 and 16/29, p=0,016). CONCLUSIONS: In this relatively large cohort, we could not confirm the association of NOD2, with rejection and graftfailure. Furthermore we found no association of seven other CD-loci with clinical endpoints. However, patients receiving a donorgraft with six or more risk alleles have decreased three-year survival, but -surprisinglyincreased rejection-free survival.