背景:微RNA(miRNA)加工机制可能通过改变miRNA表达谱来改变原发性干燥综合征(pSS)的风险。炎症细胞因子和活性氧(ROS)也参与pSS;然而,miRNA表达改变在其发病机制中的作用尚不清楚。我们旨在评估miRNA加工机制基因中的单核苷酸多态性(SNP)之间的关系,包括XPO5(RS11077),RAN(rs14035),Dicer(rs3742330),TNRC6B(rs9623117),GEMIN3(rs197412),和GEMIN4(rs2740348),和女性患者pSS的风险。还评估了细胞因子和ROS与pSS易感SNP的潜在关联。
方法:对74例女性pSS患者和77例对照者进行聚合酶链反应连接酶检测反应证实的SNPs基因分型。通过学生t检验分析关系,Wilcoxon秩和检验,卡方检验,皮尔逊相关性检验,和二元逻辑回归分析。
结果:对于GEMIN3基因的rs197412,与CT+CC携带者相比,基因型TT携带者的pSS风险增加2.172倍(比值比:2.172,95%CI,1.133~4.166,p=0.019).同时,与CT+CC基因型携带者相比,pSS易感TT携带者与干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)水平升高(P<0.001)相关(P=0.003)。随后的分析还显示IFN-γ和TNF-α水平之间存在弱正相关(r=0.271,P=0.019)。
结论:GEMIN3SNP的预测因子可能通过介导miRNAs的表达来改变女性的pSS发育,从而调节IFN-γ和TNF-α的水平。
BACKGROUND: MicroRNA (miRNA)-processing machinery may modify the risk of primary Sjögren\'s syndrome (pSS) by altering miRNA expression profiles. Inflammatory cytokines and reactive oxygen species (ROS) are also involved in pSS; however, the role of altered miRNAs expression in its pathogenesis is still unclear. We aimed to evaluate the relationship between single-nucleotide polymorphisms (SNPs) in miRNA processing machinery genes, including XPO5 (rs11077), RAN (rs14035), Dicer (rs3742330), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), and the risk of pSS in female patients. The potential associations of cytokines and ROS with pSS-susceptible SNPs were also evaluated.
METHODS: The SNPs confirmed by polymerase chain reaction ligase detection reaction were genotyped in 74 female patients with pSS and 77 controls. The relationship was analyzed by Student\'s t-test, Wilcoxon rank-sum test, chi-square test, Pearson\'s correlation test, and binary logistic regression analysis.
RESULTS: For rs197412 of the GEMIN3 gene, the genotype TT carrier was associated with a 2.172-fold increased risk for pSS when compared with that of CT+CC carrier (odds ratio: 2.172, 95% CI, 1.133-4.166, p=0.019). Simultaneously, the pSS-susceptible TT carriers were associated with increased interferon-γ (IFN-γ) (P < 0.001) and tumor necrosis factor-α (TNF-α) (P = 0.003) levels when compared with that of CT+CC genotype carriers in female patients with pSS. The subsequent analysis also showed a weak positive correlation between IFN-γ and TNF-α levels (r=0.271, P = 0.019).
CONCLUSIONS: The predictors of GEMIN3 SNPs might modify pSS development in females by mediating the expression of miRNAs and therefore regulate the levels of IFN-γ and TNF-α.