title: Genetic determinants associated with early age of diagnosis of IBD.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) is typically diagnosed at 20 to 40 years of age. However, very young versus elderly patients with IBD may have different mechanisms of disease that may affect prognosis and care.
  
  
  OBJECTIVE
  The purpose of this work was to identify single nucleotide polymorphisms associated with age of onset of Crohn's disease and ulcerative colitis.
  
  
  METHODS
  Patients were genotyped using a custom microarray chip containing 332 IBD-associated single nucleotide polymorphisms. Age at diagnosis as a continuous variable was assessed using linear regression. Patients were then subgrouped by age at diagnosis and compared by the Fisher exact test. Bonferroni correction was used in all of the analyses.
  
  
  METHODS
  This study was conducted at a tertiary academic hospital.
  
  
  METHODS
  Sixty patients with Crohn's disease and 26 with ulcerative colitis were ≤ 16 years old, 259 patients with Crohn's disease and 248 with ulcerative colitis were 17-60 years old, and 10 patients with Crohn's disease and 20 with ulcerative colitis were >60 years old at diagnosis and included in this study.
  
  
  METHODS
  Age at diagnosis and single nucleotide polymorphism correlations were measured in this study.
  
  
  RESULTS
  The NOD2 single nucleotide polymorphism rs2076756 was associated with younger age at Crohn's disease diagnosis (p = 0.0002). Patients with the AA/wild-type genotype were diagnosed at 31.9 ± 1.23 years, AG heterozygotes at 25.6 ± 0.99 years, and GG/at-risk allele homozygotes at 22.6 ± 1.32 years. Depending on age categories compared, single nucleotide polymorphisms in POU5F1, TNFSF15, and HLA DRB1*501 were associated with age of Crohn's disease diagnosis. No genetic associations were seen between ulcerative colitis and linear age at diagnosis; however, the G allele of the LAMB1 single nucleotide polymorphism rs886774 was found to be associated with ulcerative colitis diagnosed at ≤ 16 versus >17 years old (p = 0.008).
  
  
  CONCLUSIONS
  This study was limited to known IBD single nucleotide polymorphisms.
  
  
  CONCLUSIONS
  This analysis reaffirms the association between NOD2, a molecule of innate immunity, and early Crohn's disease onset. This is the first report of a possible association between early Crohn's disease and the POU5F1, TNFSF15, and HLA DRB1*501 genes. The LAMB1 gene, associated with mucosal basement membrane integrity, was associated with early onset ulcerative colitis and, thus, suggests a fundamentally different mechanism of early disease pathogenesis in ulcerative colitis versus Crohn's disease.
authors: 1 Division of Colon and Rectal Surgery, Department of Surgery, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 2 Department of Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania.
authors: Tara M
authors: TM
authors: Connelly
authors: Arthur S
authors: AS
authors: Berg
authors: Leonard
authors: L
authors: Harris
authors: David
authors: D
authors: Brinton
authors: Sue
authors: S
authors: Deiling
authors: Walter A
authors: WA
authors: Koltun
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D003424:Crohn Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*; D014481:United States
chemical_list: D059811:HLA-DRB1 Chains; C478221:LAMB1 protein, human; D007797:Laminin; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15