title: Associations between NOD2, IRGM and ORMDL3 polymorphisms and pediatric-onset inflammatory bowel disease in the Lithuanian population.
abstract: OBJECTIVE
  Recent GWAS and meta-analyses have revealed about 200 susceptibility genes/loci for inflammatory bowel diseases (IBD). However, only a small number of studies were performed in early-onset IBD. The aim of this study was to assess the association between NOD2, IL23R, ATG16L1, IRGM, IL10, NKX2-3 and ORMDL3 variants and early-onset IBD.
  
  
  METHODS
  A total of 76 affected individuals (30 with Crohn's disease [CD] and 46 with ulcerative colitis [UC]) at the age of ≤17 years and 158 matched controls recruited in Lithuania were genotyped for the known genetic susceptibility variants in NOD2 (Arg702Trp (rs2066844), Gly908Arg (rs2066845) and Leu1007insC (rs2066847)), IL23R (rs11209026), ATG16L1 (rs2241880), IRGM (rs4958847), IL10 (rs3024505), NKX2-3 (rs11190140) and ORMDL3 (rs2872507) genes.
  
  
  RESULTS
  Variants in NOD2 (Leu1007insC) and IRGM genes increased risk for CD (OR=6.56, 95% CI: 2.54-16.91, P=1.21×10-5and OR=2.32, 95% CI: 1.05-5.14, P=0.033; respectively); whereas a variant in ORMDL3 gene was strongly associated with UC (OR=1.99, 95% CI: 1.23-3.20, P=4.15×10-3).
  
  
  CONCLUSIONS
  The results confirmed that polymorphisms in NOD2 (Leu1007insC) and IRGM genes are associated with increased risk of CD; whereas the ORMDL3 variant is associated with susceptibility to UC in the Lithuanian early-onset IBD population.
authors.affiliation: Department of Paediatrics, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Gitana
authors.initials: G
authors.lastname: Pranculienė
authors.affiliation: Laboratory of Clinical and Molecular Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Rūta
authors.initials: R
authors.lastname: Steponaitienė
authors.affiliation: Laboratory of Clinical and Molecular Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Skiecevičienė
authors.affiliation: Department of Paediatrics, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Rūta
authors.initials: R
authors.lastname: Kučinskienė
authors.affiliation: Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Gediminas
authors.initials: G
authors.lastname: Kiudelis
authors.affiliation: Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Kęstutis
authors.initials: K
authors.lastname: Adamonis
authors.affiliation: Department of Paediatrics, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania. Electronic address: liut.l@takas.lt.
authors.forename: Liutauras
authors.initials: L
authors.lastname: Labanauskas
authors.affiliation: Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Limas
authors.initials: L
authors.lastname: Kupčinskas
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000453:epidemiology* / Q000235:genetics*; D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008097:Lithuania / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D008565:Membrane Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C464399:ORMDL3 protein, human; D019204:GTP-Binding Proteins; C513539:IRGM protein, human
keywords: Crohn's disease; Early onset; Inflammatory bowel diseases; Single nucleotide polymorphism; Ulcerative colitis