<i>CD244</i> is not associated with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in a Korean population

Cho, Soo-Kyung; Han, Tae Un; Kim, Kwang-Woo; Bang, So-Young; Bae, Sang Cheol; Kang, Changwon

doi:10.1002/art.24850

Cited by 6 publications

(3 citation statements)

References 44 publications

(54 reference statements)

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“…Further research is needed to elucidate the relationship between TNF and CD244 in rheumatoid arthritis. Functional SNPs (rs3766379 and rs6682654) in the CD244 gene locus are associated with RA susceptibility in European populations but not in the Korean population, which is consistent with our research ndings (OR = 1.13, 95%CI = 1.04-1.24, p = 0.006, FDR = 0.184) [37][38][39][40]. However, a previous large case-control study in the UK did not nd a relationship between rs6682654 located in CD244 locus and RA [41].…”

Section: Discussionsupporting

confidence: 89%

Exploring the causal relationship between 91 inflammatory cytokines and two subtypes of rheumatoid arthritis: a bidirectional two-sample Mendelian randomization study

Gao,

Chen,

Zheng

et al. 2024

Preprint

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Objective In previous studies, the occurrence of rheumatoid arthritis (RA) has been reported to be associated with various inflammatory cytokines. This research aims to investigate the causal relationship between 91 inflammatory cytokines and two distinct subtypes of RA, employing bidirectional two-sample Mendelian Randomization (MR) analysis. Methods Utilizing genetic summary data from a publicly available genome-wide association study (GWAS), we examined the genetic variations of 91 inflammatory cytokines in 14,824 individuals of European ancestry. RA genetic variant data were sourced from the FinnGen consortium, including 4,290 cases and 368,362 controls in the seropositive RA (SPRA) cohort, and 3,877 cases and 285,035 controls in the seronegative RA (SNRA) cohort. Primary analysis employed the Inverse Variance Weighted (IVW) method, with supplementary methods including MR Egger, Weighted Median (WM), Simple Mode, and Weighted Mode to enhance result robustness. Sensitivity analysis was conducted for result reliability. Results IVW analysis revealed elevated levels of natural killer cell receptor 2B4 (CD244), FMS-related tyrosine kinase 3 ligand (FLT3LG), interleukin (IL)-7, and tumor necrosis factor (TNF) significantly associated with an increased risk of SPRA. Lower levels of IL-6 were associated with increased risks of SNRA, while higher levels of IL-7 were related to an increased risk of SNRA. Reverse MR analysis suggested SNRA might downregulate levels of Fractalkine (CX3CL1). Conclusions This study enhances our understanding of the correlation between inflammatory cytokines and RA, providing novel insights into the etiology, diagnosis, and treatment of two RA subtypes.

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Section: Discussionsupporting

confidence: 89%

Exploring the causal relationship between 91 inflammatory cytokines and two subtypes of rheumatoid arthritis: a bidirectional two-sample Mendelian randomization study

Gao,

Chen,

Zheng

et al. 2024

Preprint

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“…Recently, a big study from South Korea failed to show the significant association between two SNPs (rs3766379 and rs6682654) and susceptibility to SLE in a Korean population [15]. Those previous studies did not investigate the association between clinical phenotypes in SLE and SNPs.…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms of CD244 gene predispose to renal and neuropsychiatric manifestations with systemic lupus erythematosus

et al. 2010

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The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) of the CD244 gene with several clinical features of systemic lupus erythematosus (SLE). Two hundred and forty-three patients with SLE and 369 healthy controls were enrolled. Two SNPs (rs6682654 and rs3766379) in the CD244 gene were determined by allelic discrimination using a specific TaqMan probe. Only SNP rs3766379 was significantly associated with susceptibility to SLE [P = 0.009; odds ratio (OR) 1.28; 95% confidence interval (CI) 1.04-1.57]. The association was preferentially observed in subsets of SLE patients with nephritis and neuropsychiatric lupus. The frequency of the rs6682654 C allele was strongly associated with nephritis and neuropsychiatric lupus (P = 0.00065; OR 1.99; 95% CI 1.34-2.95, and P = 1.6 × 10(-7); OR 3.47; 95% CI 2.12-5.70, respectively), as was the frequency of the rs3766379 T allele (P = 0.0014; OR 1.86; 95% CI 1.27-2.71, and P = 2.6 × 10(-7); OR 3.15; 95% CI 2.00-4.96, respectively). In this study, an SNP of the CD244 gene was associated with susceptibility to SLE. There was a strikingly strong association in SLE patients with nephritis and neuropsychiatric lupus, suggesting that this genetic marker could predict involvement of those severe complications.

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“…These results suggest that CD244 promotes the progression of RA. Genetic studies reported that a SNP of the CD244 gene correlated with RA susceptibility in Japanese and European Caucasian populations, but not in a Korean population (54)(55)(56). More studies are needed to clarify the function of CD244 in the initiation and progression of RA.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

Sun

Gang

et al. 2021

Front. Immunol.

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Proteins in the signaling lymphocytic activating molecule (SLAM) family play crucial roles in regulating the immune system. CD244 (SLAMF4) is a protein in this family, and is also a member of the CD2 subset of the immunoglobulin (Ig) superfamily. CD244 is a cell surface protein expressed by NK cells, T cells, monocytes, eosinophils, myeloid-derived suppressor cells, and dendritic cells. CD244 binds to the ligand CD48 on adjacent cells and transmits stimulatory or inhibitory signals that regulate immune function. In-depth studies reported that CD244 functions in many immune-related diseases, such as autoimmune diseases, infectious diseases, and cancers, and its action is essential for the onset and progression of these diseases. The discovery of these essential roles of CD244 suggests it has potential as a prognostic indicator or therapeutic target. This review describes the molecular structure and function of CD244 and its roles in various immune cells and immune-related diseases.

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CD244 is not associated with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in a Korean population

Cited by 6 publications

References 44 publications

Exploring the causal relationship between 91 inflammatory cytokines and two subtypes of rheumatoid arthritis: a bidirectional two-sample Mendelian randomization study

Exploring the causal relationship between 91 inflammatory cytokines and two subtypes of rheumatoid arthritis: a bidirectional two-sample Mendelian randomization study

Single nucleotide polymorphisms of CD244 gene predispose to renal and neuropsychiatric manifestations with systemic lupus erythematosus

Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

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