Lili Zhao,1,* Wenqi Xu,1,* Shushu Du,1,2 Fengjia Xi,1 Xiaofei Shi,3 Rongzeng Liu1 

1Department of Immunology, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2Qingpu Traditional Chinese Medicine Hospital, Shanghai, People’s Republic of China; 3Department of Rheumatology and Immunology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Rongzeng Liu, Department of Immunology, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang, People’s Republic of China, Email liurz@haust.edu.cn Xiaofei Shi, Department of Rheumatology and Immunology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, 24 Jinghua Road, Luoyang, People’s Republic of China, Email xiaofeis@haust.edu.cn

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune condition distinguished by a wide range of clinical manifestations and numerous genetic predisposition factors. The aim of the current study was to analyze the association between the IRAK1 polymorphisms (rs3027898 and rs1059702) and SLE in a Chinese cohort.
Patients and Methods: A total of 150 SLE patients and 168 healthy controls of Chinese ethnicity were included in this study. The genotyping of IRAK1 was performed using sequence-specific primers (SSP)-polymerase chain reaction. Additionally, correlations between the SNPs and clinical manifestations of SLE were evaluated.
Results: In comparison to the wild genotype CC of rs3027898, the homozygous mutation AA exhibited a significant association with a reduced risk of SLE across homozygous (AA vs CC, OR = 0.270, 95% CI = 0.086– 0.847, p = 0.017), dominant (CA+AA vs CC, OR = 0.601, 95% CI = 0.375– 0.964, p = 0.034) and recessive models (AA vs CA+CC, OR = 0.301, 95% CI = 0.097– 0.937, p = 0.029). The A allele of rs3027898 demonstrated a negative correlation with susceptibility to SLE (A vs C, OR = 0.580, 95% CI = 0.388– 0.866, p = 0.007). Furthermore, rs3027898 and rs1059702 were found to be in strong linkage disequilibrium (D′ = 0.914, r2 = 0.809). The frequency of haplotype HT2 (A/G) was significantly lower in SLE patients compared to controls (OR = 0.465, 95% CI = 0.300– 0.723, p < 0.001), while haplotype HT3 (C/G) was positively correlated with an increased susceptibility to SLE (OR = 3.838, 95% CI = 1.406– 10.480, p = 0.005).
Conclusion: The findings suggest that polymorphisms in IRAK1 are associated with a reduced risk of SLE within a Chinese demographic. These genetic variations may serve as potential biomarkers for assessing SLE risk and offer novel perspectives on the molecular mechanisms that underpin the disease.

Keywords: SLE, IRAK1, single nucleotide polymorphism, haplotype, TLR signaling pathway