SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population

Abstract

Objectives A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene. Methods The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis. Result For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16–1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT. Conclusions SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.

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

“…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 ). An analysis showed that mRNA expression of the inflammasome genes NOD-like receptor family pyrin domain containing 3 ( NLRP3 ) and caspase recruitment domain-containing protein 8 ( CARD8 ) in the PBMCs of 230 RA patients from two different populations was correlated with susceptibility and RA progression ( p = 0.044) and with severity ( p = 0.03), respectively; in addition, the NLRP3 expression levels were also significantly elevated ( 71 ).…”

Role of signaling lymphocytic activation molecule family of receptors in the pathogenesis of rheumatoid arthritis: insights and application

“…Which underscored the importance of the immune system as well as non-immune tissues for the development of RA (Kwon et al, 2020). Xia et al (2022) analyzed the expression of Frontiers in Pharmacology frontiersin.org SLAMF6 gene in synovial tissue of RA patients and in the control group. The expression of SLAMF6 was significantly higher in RA patients than that in the control group.…”

Identifying functional subtypes and common mechanisms of rheumatoid arthritis and systemic lupus erythematosus

“…2b-d). Then 25 different cell clusters were grouped into seven cell types including T cells (0, 1,4,5,8,11,12,16,20), NK cells (7), B cells (6, 10,18,19), monocytes (2,3,13,15,17), neutrophils (9,21,23), megakaryocytes (14), and DC cells (22,24) by using UMAP clustering analysis (Fig. 2a).…”

“…Researchers have also identi ed a functional variant of SLAMF6 gene (rs148363003) that is associated with susceptibility to and severity of RA. Moreover, inhibition of the SLAMF6 signaling pathway has been shown to alleviate arthritis symptoms [20] . These results suggest that SLAMF6 plays an important role in the pathophysiological processes of RA and is considered a potential therapeutic target.…”