Burghardt Karolina Maria, Avinashi Vishal, Kosar Christina, Xu Wei, Wales Paul W, Avitzur Yaron, Muise Aleixo
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.
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, BC Children Hospital, Vancouver, British Columbia, Canada.
PLoS One. 2014 Jan 21;9(1):e85915. doi: 10.1371/journal.pone.0085915. eCollection 2014.
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.
最近，已报道了肠道移植中的基因关联。具体而言，据报道，克罗恩病易感基因NOD2多态性在肠道移植（IT）后发生移植失败的患者中更为普遍。因此，我们试图确定NOD2信号级联中的多态性，包括NOD2、CARD9、RAC1和ATG16L1是否与肠衰竭（IF）或其并发症相关。我们对59例IF患儿和500名健康的白种人对照进行了一项横断面研究。使用Taqman平台，我们确定了NOD2以及ATG16L1、RAC1和CARD9单核苷酸多态性（SNP）的流行情况。评估了NOD2途径多态性与败血症发作、入住重症监护病房（ICU）、高胆红素血症以及IT需求的结局之间的关系。我们发现，与健康对照相比，CARD9 SNP的次要等位基因与预防IF的发生相关，并且还与持续性结合胆红素血症几率的降低相关。因此，具有CARD9多态性的IF患者发生进行性肝病的可能性较小，这表明宿主固有免疫可能在IF相关肝病中起作用。
