# TNF-alpha Promoter Single-Nucleotide Polymorphisms and Inflammatory Bowel Diseases in Romania: Association with Disease Susceptibility and Clinical Features

## TL;DR

This study explores how genetic variations in the TNF-alpha gene affect the risk and features of inflammatory bowel diseases in Romania.

## Contribution

The study identifies specific genetic variants linked to disease susceptibility and clinical features in Romanian IBD patients.

## Key findings

- The rs361525 A allele is more common in Crohn’s disease patients than in healthy controls.
- The rs1800629 A allele is strongly associated with extraintestinal manifestations in both Crohn’s and ulcerative colitis.
- Genetic variants in TNF-alpha are linked to disease extension in ulcerative colitis patients.

## Abstract

Background/Objectives: Tumor necrosis factor alpha (TNF-alpha) plays a key role in systemic inflammation in multiple disorders, including inflammatory bowel diseases (IBDs). Our purpose was to investigate the contribution of two promoter single-nucleotide polymorphisms (rs361525/–238G/A and rs1800629/–308G/A) to disease susceptibility, clinical features, and response to biologic therapy in a cohort of Romanian patients with IBDs. Methods: A total of 198 patients with IBDs, 106 with Crohn’s disease (CD) and 92 with ulcerative colitis (UC), as well as 160 healthy controls, all Caucasians of Romanian origin, were genotyped using TaqMan Allelic Discrimination Assays. Phenotypical and anti-TNF treatment characteristics of the patients with IBDs were recorded. Statistical analyses were performed using OpenEpi and PLINK v1.07 software. Results: We found a significantly higher frequency of the minor allele A of rs361525 in patients with CD than in the controls (6.6% vs. 2.2%, p = 0.01, OR = 3.16). Half of the patients with extraintestinal manifestations (EIMs) had at least one copy of the rs1800629 A allele compared with approximately 10% of patients without EIM (p = 1 × 10−4, OR 9.58 for UC and p = 9 × 10−4, OR 6.60 for CD). In the whole IBD group of patients, the carriers of the minor allele (AA+GA) for both SNPs studied (rs1800629 and rs361525) were significantly more likely to have EIM associated with IBDs (p = 3 × 10−7, OR 7.87; p = 0.03, OR 3.02, respectively). In patients with UC, the analysis according to disease extension revealed that the frequency of the minor allele of rs1800629 was significantly higher in the subgroup with the E2 phenotype compared to the E1 and E3 phenotypes (16.6% versus 5.6%, p = 0.02, OR 3.32). Conclusions: These findings highlight the role of genetic TNF-alpha variants in disease susceptibility, phenotype, and systemic involvement, supporting their potential relevance in understanding IBD heterogeneity.