Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expression Level in Rheumatoid Arthritis

Abstract

Objectives. The aim of our study was to investigate the association of single-nucleotide polymorphism (SNP) and mRNA expression profile of single immunoglobulin IL-1-related receptor (SIGIRR) in rheumatoid arthritis (RA) in a Chinese population. Methods. SIGIRR rs7396562 polymorphism was genotyped using TaqMan allelic discrimination assay in 517 RA patients and 601 healthy controls. Simultaneously, the SIGIRR mRNA expression levels of 79 RA patients and 76 healthy controls were examined by real-time quantitative polymerase chain reaction (RT-qPCR). Results. The frequency of SIGIRR rs7396562 T allele was significantly higher in RA patients compared with healthy controls (T versus G: OR = 1.277 , 95 % CI = 1.079 − 1.511 , P = 0.004 ). The TT genotype of SIGIRR rs7396562 was more frequent in RA patients than in healthy controls ( OR = 1.547 , 95 % CI = 1.107 − 2.163 , P = 0.011 ). Moreover, we also found a significant difference in the recessive model (TT versus TG+GG: OR = 1.439 , 95 % CI = 1.122 − 1.847 , P = 0.004 ). However, no significant evidence was observed for the association of the SIGIRR rs7396562 with RA in dominant model (TT+TG versus GG: OR = 1.275 , 95 % CI = 0.947 − 1.717 , P = 0.109 ). Further analysis showed no association between SIGIRR rs7396562 polymorphism and laboratory parameters of RA patients (all P > 0.05 ). The mRNA expression of SIGIRR was decreased in PBMCs of patients with RA when compared to healthy controls ( Z = − 2.459 , P = 0.014 ). No significant differences in SIGIRR mRNA expression levels were observed in patients with RA with different genotypes ( P = 0.280 ). Conclusions. Our findings demonstrated that the dysregulation of SIGIRR might be associated with the pathogenesis of RA, and SIGIRR rs7396562 polymorphism might contribute to RA susceptibility in the Chinese population.

IL-1R8 as Pathoimmunological Marker for Severity of Canine Chronic Enteropathy

“…An association was uncovered between IL-1R8 expression level and dog breed, which could be related to specific polymorphisms of the gene in different populations of dogs [36,37].…”

SIGIRR deficiency contributes to CD4 T cell abnormalities by facilitating the IL1/C/EBPβ/TNF-α signaling axis in rheumatoid arthritis

“…Memory CD4 T cells are of great interest in the context of autoimmune diseases because of their long-lived nature, efficient responses to antigens, and unique potential to mediate recurring autoimmune responses (Raphael et al 2020). Based on the relatively higher expression of the SIGIRR gene on human memory CD4 T cells or CD4 T cells predicted by single-cell or bulk transcriptomic analysis, memory CD4 T cells were focused on demonstrating the functions of SIGIRR in RA, although gene polymorphisms and the regulation of SIGIRR in rheumatoid arthritis have been reported in earlier studies (Drexler et al 2010;Yang et al 2021). We observed an aberrant downregulation of SIGIRR and enhanced TNF-α production in memory CD4 T cells from the peripheral blood of RA patients and found that SIGIRR deficiency promoted the progression of AIA mediated by elevated TNF-α expression, thus establishing a closer association between SIGIRR and TNF-α production in memory CD4 T cells in RA for the first time.…”

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

“…Therefore, HDAC mRNA might play an essential role in the pathogenesis of RA ( 68 ). The single immunoglobulin IL-1-related receptor (SIGIRR) mRNA expression was decreased in the PBMCs of RA patients in a study including 79 such patients, and SIGIRR dysregulation might be related to RA pathogenesis and susceptibility ( 69 ). In a recently published study of 650 patients with RA, signaling lymphocyte activation molecule family 6 (SLAMF6) expression in the synovial tissue was 1.6-fold higher than in the controls and correlated with the severity and susceptibility of RA ( 70 ).…”