A CARD9 polymorphism is associated with decreased likelihood of persistent conjugated hyperbilirubinemia in intestinal failure.
Recently, genetic associations have been described in intestinal transplants. Namely, Crohn's disease susceptibility gene NOD2 polymorphisms have been reported to be more prevalent in patients with graft failure following intestinal transplantation (IT). Therefore, we sought to determine if polymorphisms in the NOD2 signaling cascade, including NOD2, CARD9, RAC1 and ATG16L1 are associated with intestinal failure (IF) or its complications. We carried out a cross-sectional study of 59 children with IF and 500 healthy Caucasian controls. Using the Taqman platform we determined the prevalence of NOD2 as well as ATG16L1, RAC1 and CARD9 SNPs. NOD2 pathway polymorphisms were evaluated in relation to outcomes of episodes of sepsis, ICU admissions, hyperbilirubinemia and need for IT. We found that the minor allele of a CARD9 SNP was associated with protection from developing IF when compared to healthy controls and was also associated with decreased odds of sustained conjugated hyperbilirubinemia. Therefore, IF patients with CARD9 polymorphism are less likely to develop progressive liver disease and suggests that host innate immunity may play a role in IF associated liver disease.
Group for Improvement of Intestinal Function and Treatment (GIFT), Transplant Centre, Toronto, Ontario, Canada ; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Toronto, Ontario, Canada.
Karolina Maria
KM
Burghardt
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, BC Children Hospital, Vancouver, British Columbia, Canada.
Vishal
V
Avinashi
Group for Improvement of Intestinal Function and Treatment (GIFT), Transplant Centre, Toronto, Ontario, Canada.
Christina
C
Kosar
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Wei
W
Xu
Group for Improvement of Intestinal Function and Treatment (GIFT), Transplant Centre, Toronto, Ontario, Canada.
Paul W
PW
Wales
Group for Improvement of Intestinal Function and Treatment (GIFT), Transplant Centre, Toronto, Ontario, Canada ; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Toronto, Ontario, Canada.
Yaron
Y
Avitzur
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Toronto, Ontario, Canada ; SickKids IBD Centre, Program in Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Aleixo
A
Muise
D000293:Adolescent; D000071183:Autophagy-Related Proteins; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D006932:Hyperbilirubinemia / Q000235:genetics*; D007223:Infant; D007422:Intestines / Q000473:pathology*; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome; D020830:rac1 GTP-Binding Protein / Q000235:genetics
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D002352:Carrier Proteins; D053473:Nod2 Signaling Adaptor Protein; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein