Detection and Functional Evaluation of −262A/T and −188A/G Polymorphisms of SLAM Gene in Patients with Systemic Lupus Erythematosus
Detection and Functional Evaluation of −262A/T and −188A/G Polymorphisms of SLAM Gene in Patients with Systemic Lupus Erythematosus
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DOI：
10.3899/jrheum.091390
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发表时间：
2010-11
期刊：
影响因子：
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通讯作者：
Y. You;Zhe Wang;Guowei Deng;Yi Liu;F. Hao
中科院分区：
文献类型：
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作者：
Y. You;Zhe Wang;Guowei Deng;Yi Liu;F. Hao
客观的。信号淋巴细胞激活分子 (SLAM) 通过调节 T 细胞依赖性体液免疫反应与系统性红斑狼疮 (SLE) 的病理学相关。我们研究了中国 SLE 患者 SLAM -262A/T 和 -188A/G 多态性的功能关联。方法。对 248 例病例和 278 例对照进行了 SLAM 中 -262A/T (rs2295614) 和 -188A/G (rs2295613) 的基因分型。使用双荧光素酶报告系统评估 SLAM 基因上单倍型的启动子活性。采用实时聚合酶链式反应测定不同基因型SLE患者外周血单个核细胞（PBMC）上SLAM mRNA的表达量。结果。 SLE 患者中 -262A 等位基因和 -188G 等位基因的频率显着高于对照组。单倍型分析和多因素逻辑回归分析表明，具有 AG/AG 单倍型的个体对 SLE 的易感性增加（p = 0.002，OR 1.478，95% CI 1.152–1.897）。响应PHA刺激，与-262A-188G杂合子和具有其他基因型的个体相比，-262A-188G单倍型纯合子中SLE患者PBMC上的SLAM mRNA表达显着更高。结论。我们的研究结果表明，SLAM 基因启动子中的−262A-188G 单倍型通过增加 SLAM 的表达来增加 SLE 的风险。
Objective. Signaling lymphocytic activation molecule (SLAM) has been related to the pathology of systemic lupus erythematosus (SLE) through regulation of T cell-dependent humoral immune responses. We investigated the functional associations of the −262A/T and −188A/G polymorphisms of SLAM in Chinese patients with SLE. Methods. Genotyping of −262A/T (rs2295614) and −188A/G (rs2295613) in SLAM was carried out in 248 cases and 278 controls. Promoter activities of haplotypes on the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients with different genotypes were determined by real-time polymerase chain reaction. Results. Frequencies of −262A allele and −188G allele were significantly higher in SLE patients than in controls. Haplotype analysis and multifactorial logistic regression analysis showed that individuals with the AG/AG haplotype had increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152–1.897). In response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was significantly higher in −262A-188G haplotype homozygotes compared with −262A-188G heterozygotes and individuals with other genotypes. Conclusion. Our findings suggest that −262A-188G haplotype in the SLAM gene promoter contributes to the risk of SLE by increasing the expression of SLAM.