Zhao Lili, Du Shushu, Xu Wenqi, Shi Xiaofei, Liu Rongzeng
Department of Immunology, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, China.
Qingpu Traditional Chinese Medicine Hospital, Shanghai, China.
PeerJ. 2025 Aug 13;13:e19847. doi: 10.7717/peerj.19847. eCollection 2025.
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 AA, OR = 1.79, 95% CI [1.07-2.99], = 0.025), homozygous (GG AA, OR = 2.11, 95% CI [1.06-4.19], = 0.033), dominant (GG+AG AA, OR = 1.86, 95% CI [1.15-3.03], = 0.012), and allele (G A, OR = 1.49, 95% CI [1.07-2.06], = 0.017) models. Similarly, rs352140 was significantly associated with SLE risk in homozygous (TT CC, OR = 2.47, 95% CI [1.23-4.96], = 0.010), recessive (TT CC+CT, OR = 2.57, 95% CI [1.35-4.88], = 0.003), and allele (T C, OR = 1.43, 95% CI [1.03-1.99], = 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], = 0.030), while haplotype HT2 (T/G/T) was positively associated with increased susceptibility (OR = 1.505, 95% CI [1.068-2.121], = 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.
TLR9基因变异与多种自身免疫性疾病相关，但TLR9基因多态性与系统性红斑狼疮（SLE）之间的关系仍存在争议。本研究旨在评估TLR9基因内三个单核苷酸多态性（SNP）与中国汉族女性人群SLE易感性之间的潜在关联。
共纳入150例SLE患者和151例中国汉族健康对照。采用序列特异性引物（SSP）聚合酶链反应对TLR9进行基因分型，并通过桑格测序进行验证。使用卡方检验或费舍尔精确检验分析SNP与SLE易感性之间的关联。此外，评估SNP与SLE临床表现之间的相关性。
TLR9 rs352139多态性在杂合子（AG对AA，OR = 1.79，95%CI[1.07 - 2.99]，P = 0.025）、纯合子（GG对AA，OR = 2.11，95%CI[1.06 - 4.19]，P = 0.033）、显性（GG + AG对AA，OR = 1.86，95%CI[1.15 - 3.03]，P = 0.012）和等位基因（G对A，OR = 1.49，95%CI[1.07 - 2.06]，P = 0.017）模型中与SLE易感性增加显著相关。同样，rs352140在纯合子（TT对CC，OR = 2.47，95%CI[1.23 - 4.96]，P = 0.010）、隐性（TT对CC + CT，OR = 2.57，95%CI[1.35 - 4.88]，P = 0.003）和等位基因（T对C，OR = 1.43，95%CI[1.03 - 1.99]，P =
