Review article: Inflammatory bowel disease and genetics.

Area of Science:

• Gastroenterology
• Genetics
• Immunology

Background:

• Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a complex multigenic disorder.
• Significant advancements have been made in identifying the genetic underpinnings of IBD.
• Mutations in the NOD2 gene are associated with ileal Crohn's disease, and other susceptibility genes have been discovered.

Purpose of the Study:

• To review the current understanding of the genetic background of inflammatory bowel disease.
• To explore the role of identified genes, such as NOD2, in IBD pathogenesis.
• To highlight the need for further research in genetic factors influencing IBD.

Main Methods:

• A comprehensive literature review was conducted.
• The review focused on studies investigating the genetic basis of IBD.
• Data from mouse models, in vitro experiments, and human studies were considered.

Main Results:

• The precise functional impact of NOD2 mutations in Crohn's disease remains incompletely understood, with conflicting data on its role (loss or gain of function).
• Several additional genes and the IBD5 locus (including SLC22A4/5) have been linked to IBD susceptibility.
• Only a subset of identified genes are currently recognized as significant disease-causing or modifying factors.

Conclusions:

• While genetic research has not yet enabled precise disease course prediction or therapy selection, it has substantially improved understanding of IBD pathogenesis.
• Accurate patient phenotyping and large, population-based cohorts are crucial for future genetic investigations.
• Continued genetic research holds promise for classifying IBD phenotypes molecularly and developing novel therapeutic strategies.