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

Background 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 polymorph...

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Main Authors: Lili Zhao, Shushu Du, Wenqi Xu, Xiaofei Shi, Rongzeng Liu
Format: Article
Language:English
Published: PeerJ Inc. 2025-08-01
Series:PeerJ
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Online Access:https://peerj.com/articles/19847.pdf
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author Lili Zhao
Shushu Du
Wenqi Xu
Xiaofei Shi
Rongzeng Liu
author_facet Lili Zhao
Shushu Du
Wenqi Xu
Xiaofei Shi
Rongzeng Liu
author_sort Lili Zhao
collection DOAJ
description Background 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. Methods 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. Results 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). Conclusions 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.
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spelling doaj-art-7fef8c7e1d59437cb0675955fe16c11b2025-08-20T03:38:18ZengPeerJ Inc.PeerJ2167-83592025-08-0113e1984710.7717/peerj.19847Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patientsLili Zhao0Shushu Du1Wenqi Xu2Xiaofei Shi3Rongzeng Liu4Department of Immunology, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, ChinaDepartment of Immunology, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, ChinaDepartment of Immunology, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, ChinaDepartment of Immunology, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, ChinaBackground 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. Methods 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. Results 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). Conclusions 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.https://peerj.com/articles/19847.pdfSLETLR9Single nucleotide polymorphismSusceptibility
spellingShingle Lili Zhao
Shushu Du
Wenqi Xu
Xiaofei Shi
Rongzeng Liu
Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients
PeerJ
SLE
TLR9
Single nucleotide polymorphism
Susceptibility
title Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients
title_full Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients
title_fullStr Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients
title_full_unstemmed Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients
title_short Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients
title_sort genetic variants of toll like receptor 9 are associated with susceptibility to systemic lupus erythematosus in han chinese female patients
topic SLE
TLR9
Single nucleotide polymorphism
Susceptibility
url https://peerj.com/articles/19847.pdf
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