title: Variations in inflammatory genes as molecular markers for prediction of inflammatory bowel disease occurrence.
abstract: OBJECTIVE
  Research on inflammatory bowel disease (IBD) has highlighted genes involved in the regulation of inflammatory responses as contributors to disease pathogenesis. This study aimed to evaluate the associations between IBD and variations in NOD2, TLR4, TNF-α, IL-6, IL-1β and IL-1RN genes, and to use the genetic data obtained in predictive modeling.
  
  
  METHODS
  A total of 167 IBD patients and 101 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Using the genotype data attained as the input to various classification algorithms, IBD prediction models were designed. The area under the receiver operating characteristic curve (AUROC) was used to measure their performance.
  
  
  RESULTS
  Significant associations were found between Crohn's disease (CD) and minor NOD2 variants, as well as TLR4 299Gly, TNF-α G-308A, IL-6 G-174C and IL-1RN VNTR A2 variants, while ulcerative colitis (UC) was associated only with IL-1RN VNTR A2 variants. CD and UC showed highly significant difference in the allelic distribution of TNF-α G-308A, where the A allele was found to be related to CD, and the G allele to UC. A combined effect of patients' gender and TLR4 variants was observed among CD patients. When all analyzed genotype and gender data were used, prediction performance achieved a maximum AUROC of 0.690 for CD and 0.601 for UC dataset.
  
  
  CONCLUSIONS
  Variations in the genes involved in immune regulation are genetic factors of importance in IBD susceptibility that could potentially be used as predictors of disease development.
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors: Biljana
authors: B
authors: Stankovic
authors: Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.
authors: Sanja
authors: S
authors: Dragasevic
authors: School of Medicine, University of Belgrade, Belgrade, Serbia.|Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.
authors: Dragan
authors: D
authors: Popovic
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors: Branka
authors: B
authors: Zukic
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors: Nikola
authors: N
authors: Kotur
authors: School of Medicine, University of Belgrade, Belgrade, Serbia.|Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.
authors: Aleksandra
authors: A
authors: Sokic-Milutinovic
authors: School of Medicine, University of Belgrade, Belgrade, Serbia.|Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.
authors: Tamara
authors: T
authors: Alempijevic
authors: School of Medicine, University of Belgrade, Belgrade, Serbia.|Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.
authors: Snezana
authors: S
authors: Lukic
authors: School of Medicine, University of Belgrade, Belgrade, Serbia.|Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia.
authors: Tomica
authors: T
authors: Milosavljevic
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors: Gordana
authors: G
authors: Nikcevic
authors: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors: Sonja
authors: S
authors: Pavlovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000235:genetics*; D003424:Crohn Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D053473:Nod2 Signaling Adaptor Protein / Q000097:blood / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D055771:Serbia; D012737:Sex Factors; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; C507763:IL1RN protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: Serbian cohort; genetic variant; inflammatory bowel disease; inflammatory gene; predictive modeling