Variations in inflammatory genes as molecular markers for prediction of inflammatory bowel disease occurrence. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Stankovic, Biljana; Dragasevic, Sanja; Popovic, Dragan; Zukic, Branka; Kotur, Nikola; Sokic‐Milutinovic, Aleksandra; Alempijevic, Tamara; Lukic, Snezana; Milosavljevic, Tomica; Nikcevic, Gordana; Pavlovic, Sonja
• Is Part Of: Journal of digestive diseases. Volume 16:Issue 12(2015:Dec.)
• Page Start: 723
• Page End: 733
• Publication Date: 2015-12
• Subjects: genetic variant -- inflammatory bowel disease -- inflammatory gene -- predictive modeling -- Serbian cohort; Digestive organs -- Diseases -- Periodicals; Gastroenterology -- Periodicals; 616.3
• DOI: 10.1111/1751-2980.12281
• Languages: English
• ISSNs: 1751-2972

Abstract

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. Conclusion: 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.