# Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients

## TL;DR

This study finds that specific genetic variations in the TLR9 gene are linked to a higher risk of developing systemic lupus erythematosus in Han Chinese women.

## Contribution

The study identifies two TLR9 gene polymorphisms associated with SLE susceptibility in Han Chinese females.

## Key findings

- The TLR9 rs352139 polymorphism increases SLE risk in multiple genetic models.
- The TLR9 rs352140 polymorphism is significantly linked to SLE susceptibility.
- Haplotype HT2 (T/G/T) is associated with increased SLE risk, while HT1 (C/A/T) is protective.

## Abstract

Variations in the TLR9 gene have been associated with several autoimmune disorders, but the relationship between TLR9 polymorphisms and systemic lupus erythematosus (SLE) remains controversial. This study aims to evaluate the potential association between three single-nucleotide polymorphisms (SNPs) within the TLR9 gene and susceptibility to SLE in the Han Chinese female population.

A total of 150 SLE patients and 151 healthy controls of Han Chinese ethnicity were enrolled. Genotyping of TLR9 was performed using sequence-specific primer (SSP) polymerase chain reaction and validated by Sanger sequencing. Associations between the SNPs and SLE susceptibility were analyzed using the chi-square test or Fisher’s exact test. Additionally, correlations between the SNPs and clinical manifestations of SLE were assessed.

The TLR9 rs352139 polymorphism was significantly associated with increased SLE susceptibility in heterozygous (AG vs. AA, OR = 1.79, 95% CI [1.07–2.99], p =  0.025), homozygous (GG vs. AA, OR = 2.11, 95% CI [1.06–4.19], p =  0.033), dominant (GG+AG vs. AA, OR = 1.86, 95% CI [1.15–3.03], p =  0.012), and allele (G vs. A, OR = 1.49, 95% CI [1.07–2.06], p =  0.017) models. Similarly, rs352140 was significantly associated with SLE risk in homozygous (TT vs. CC, OR = 2.47, 95% CI [1.23–4.96], p =  0.010), recessive (TT vs. CC+CT, OR = 2.57, 95% CI [1.35–4.88], p =  0.003), and allele (T vs. C, OR = 1.43, 95% CI [1.03–1.99], p =  0.031) models. Haplotype analysis revealed that haplotype HT1 (C/A/T) had a protective effect against SLE (OR = 0.70, 95% CI [0.506–0.966], p =  0.030), while haplotype HT2 (T/G/T) was positively associated with increased susceptibility (OR = 1.505, 95% CI [1.068–2.121], p =  0.019).

These findings suggest that the TLR9 rs352139 and rs352140 polymorphisms are significantly associated with increased susceptibility to SLE in the Han Chinese population, indicating a potential role of TLR9 in the pathogenesis of SLE.