# Associations between TNF gene promoter variants (rs361525, rs1800629, rs1799964, rs1799724) and the clinical course of idiopathic inflammatory myopathies

## TL;DR

This study explores how specific genetic variations in the TNF gene are linked to the risk and symptoms of idiopathic inflammatory myopathies.

## Contribution

The study identifies specific TNF gene promoter variants associated with disease susceptibility and clinical features in IIM patients.

## Key findings

- The rs1800629 AG genotype is linked to increased IIM susceptibility and interstitial lung disease.
- The rs1799964 TT genotype is associated with interstitial lung disease and anti-Jo1 antibodies.
- The rs1799724 CT genotype is connected to skin manifestations like Gottron and shawl signs.

## Abstract

Idiopathic inflammatory myopathies (IIM) are characterized by muscle weakness and immune-mediated muscle injury. Tumor necrosis factor (TNF) appears to be involved in the pathogenesis of IIM, especially regarding susceptibility to malignancy. Here, we analyzed associations between variants of the TNF gene promoter and the clinical course of the disease. We conducted a case–control study that analyzed selected variants of the TNF gene promoter (rs361525, rs1800629, rs1799964, rs1799724) in 56 stable IIM patients using commercially available TaqMan allelic discrimination assays with real-time PCR. Clinical and laboratory data were collected to evaluate associations between genotypes and disease manifestations. Control subjects (n = 38) matched for sex and without a medical history of connective tissue diseases were included for comparison. The variant rs1800629 was the only one associated with increased susceptibility to the disease (p = 0.010), with a higher frequency of the AG genotype in the IIM group compared to controls. The same genotype (rs1800629 AG) was also associated with interstitial lung disease (ILD) in the patients (p = 0.024). Furthermore, ILD was related to the rs1799964 TT genotype (p = 0.049), which was also more frequent in those with anti-Jo1 antibodies (p = 0.012). The CT variant rs1799724 was associated with skin manifestations, such as the Gottron sign (p = 0.030) and the shawl sign (p = 0.021). No significant relationship was documented for the promoter variant of the rs361525 TNF gene. Our study revealed associations of specific variants of the TNF gene promoter with susceptibility to IIM and clinical manifestations of the disease. Extensive observational studies are needed to verify our findings.

The online version contains supplementary material available at 10.1038/s41598-025-25258-z.