# Analysis of TNFAIP3, IRAK1, and TLR4 Gene Polymorphisms in Patients With Rheumatoid Arthritis

**Authors:** Zhenboyang Tang, Lihui Peng, Zixia Zhao, Xiping Zhou, Xiru Ling, Chunyan Huang, Jiqiang Wu, Ping Wang, Jie Chen

PMC · DOI: 10.1002/iid3.70344 · 2026-02-12

## TL;DR

This study found that certain gene variations in TNFAIP3, IRAK1, and TLR4 are linked to a higher or lower risk of developing rheumatoid arthritis.

## Contribution

The study identifies specific gene polymorphisms in TNFAIP3, IRAK1, and TLR4 that are associated with rheumatoid arthritis susceptibility.

## Key findings

- The IRAK1 rs1059703 A allele and TNFAIP3 rs5029930 C allele and AC genotype are associated with lower rheumatoid arthritis risk.
- The TNFAIP3 rs5029939 C allele and TLR4 rs7873784 C allele and CG genotype are associated with higher rheumatoid arthritis risk.

## Abstract

Rheumatoid arthritis (RA) arises from a complex interplay of polygenic susceptibility, epigenetic factors, and environmental modifiers. This study investigated the correlation between RA and Tumor necrosis factor α‐induced protein 3 (TNFAIP3), Interleukin‐1 receptor‐associated kinase 1 (IRAK1), and Toll‐like receptor 4 (TLR4) gene polymorphisms.

A sample of 308 RA cases and 310 matched controls was included. Genotyping of the TNFAIP3, IRAK1, and TLR4 was performed via mass spectrometry.

Compared to healthy controls, individuals carrying the rs1059703 A allele (odds ratio (OR) = 0.640, 95% confidence interval (CI): 0.458–0.895, p = 0.009) of IRAK1, individuals carrying the rs5029930 C allele (OR = 0.469, 95% CI: 0.298–0.739, p = 0.001), and AC genotype (OR = 0.427, 95% CI: 0.255–0.716, p = 0.001) of TNFAIP3 had a lower RA risk. Individuals carrying the rs5029939 C allele (OR = 2.401, 95% CI: 1.436–4.017, p = 0.001) of TNFAIP3, individuals carrying the rs7873784 C allele (OR = 1.549, 95% CI: 1.101–2.179, p = 0.012), and CG genotype (OR = 1.489, 95% CI: 1.011–2.193, p = 0.043) of TLR4 had a higher RA risk.

In summary, the TNFAIP3, IRAK1, and TLR4 gene polymorphisms are associated with RA susceptibility.

## Linked entities

- **Genes:** TNFAIP3 (TNF alpha induced protein 3) [NCBI Gene 7128], IRAK1 (interleukin 1 receptor associated kinase 1) [NCBI Gene 3654], TLR4 (toll like receptor 4) [NCBI Gene 7099]
- **Diseases:** Rheumatoid Arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IRAK1 (interleukin 1 receptor associated kinase 1) [NCBI Gene 3654] {aka IRAK, pelle}, TNFAIP3 (TNF alpha induced protein 3) [NCBI Gene 7128] {aka A20, AIFBL1, AISBL, OTUD7C, TNFA1P2}
- **Diseases:** RA (MESH:D001172)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs5029930, rs5029939, rs1059703, rs7873784

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12902183/full.md

---
Source: https://tomesphere.com/paper/PMC12902183