Department of Orthopaedic Surgery, The JiangYan TCM Hospital of Taizhou City, JiangYan Road No. 699, Taizhou City, 225500, China.
Department of Orthopaedic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei City, China.
J Orthop Surg Res. 2022 Jan 11;17(1):13. doi: 10.1186/s13018-021-02901-9.
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.
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.
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.
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.
最近发表的一项全基因组关联研究鉴定了与韩国人群类风湿关节炎（RA）相关的六个新的基因位点。我们旨在探讨这些新报道的 RA 风险基因座是否与中国人群中的 RA 相关，并进一步描述易感基因的功能作用。
在 600 例 RA 患者和 800 例健康对照中，对 RA 的易感变异进行基因分型，包括 SLAMF6 的 rs148363003、CXCL13 的 rs117605225、SWAP70 的 rs360136、NFKBIA 的 rs111597524、ZFP36L1 的 rs194757 和 LINC00158 的 rs1547233。对 50 例 RA 患者和 40 例无骨关节炎的对照者的膝关节滑膜组织进行基因表达分析。对基因分型数据采用卡方检验，对基因表达分析采用 Student's t 检验进行组间比较。
对于 SLAMF6 的 rs148363003，与对照组相比，RA 患者的 CC 基因型（4.5%比 0.9%，p=0.004）频率显著降低。患者中 C 等位基因的频率明显高于对照组（11.5%比 8.0%，p=0.002），比值比为 1.49（95%可信区间为 1.16-1.92）。在其他 5 个变体中，患者与对照组的基因型或等位基因频率无显著差异。与对照组相比，RA 患者的 SLAMF6 mRNA 表达水平高 1.6 倍。此外，与 TT 基因型患者相比，CC 基因型患者的 SLAMF6 表达水平高 1.5 倍。
SLAMF6 与中国人群 RA 的易感性和严重程度均相关。此外，rs148363003 可能是调节 RA 患者 SLAMF6 组织表达的功能性变异。为了全面了解该变异对 RA 发病的贡献，建议进行进一步的功能分析。
