BACKGROUND:More and more studies demonstrated that genetic variation at C1GALT1 influences Gd-IgA1 level in IgAN. However, whether the expression of β1, 3-galactosyltransferase (β1, 3Gal-T) was influenced may provide insights into how Gd-IgA1 levels are controlled in IgAN. METHODS:Thirty IgAN patients diagnosed in Tianjin Medical University General Hospital from April to September 2018 and 30 healthy volunteers whose age and gender matched with patients were enrolled in this study. Total Gd-IgA1 levels in plasma were determined by ELISA and C1GALT1 levels were determined by RT-PCR. Four databases (PubMed, EMBASE, CNKI, WanFang Medical Network) were searched to identify eligible studies that evaluated a difference in the expression of C1GALT1 in IgAN patients compared with total controls (non-IgAN and health controls). The C1GALT1C1 expression levels, which was indispensable to β1, 3Gal-T of IgA1, was also been compared. RESULTS:Gd-IgA1 levels were remarkable higher in IgAN patients compared with healthy control. The expression levels of C1GALT1 gene were remarkably down-regulated in IgAN patients compared with healthy control. And the mRNA level of C1GALT1 was inversely correlated to Gd-IgA1 levels. In meta-analysis, six articles including 316 participants that analyzed the expression of β1, 3Gal-T were met inclusion criteria. There was no significant difference in the expression of C1GALT1 between IgAN patients compared with controls. And we found patients with IgAN had lower levels of C1GALT1 gene expression in the B cells compared to controls. The C1GALT1C1 levels in the IgAN patients were not different from the levels in the control group, which were unchanged no matter according to different ethnic population, different control group and different cell source. Two studies including 46 persons compared enzymatic activity of β1, 3Gal-T in B cells, and the result showed the β1, 3Gal-T activity was decreased in B cells. CONCLUSIONS:We found expression levels of C1GALT1 were remarkably downregulated in IgAN patients and negatively correlated with higher levels of Gd-IgA1. Subsequent meta-analysis validated the low expression and activity of β1, 3Gal-T in B cells in patients with IgAN. However, there was no apparent disparity in the aspect of C1GALT1C1 expression between IgAN and control groups.

译文

背景:越来越多的研究表明,C1GALT1的遗传变异会影响IgAN中的Gd-IgA1水平。但是,是否影响了β1、3-半乳糖基转移酶(β1、3Gal-T)的表达,可以提供有关如何在IgAN中控制Gd-IgA1水平的见解。
方法:纳入2018年4月至2018年9月在天津医科大学总医院诊断的30例IgAN患者和30名年龄和性别与患者相匹配的健康志愿者。通过ELISA测定血浆中总Gd-IgA1水平,通过RT-PCR测定C1GALT1水平。搜索四个数据库(PubMed,EMBASE,CNKI,万方医学网)以鉴定合格的研究,这些研究评估了IgAN患者与总对照(非IgAN和健康对照)相比C1GALT1表达的差异。还比较了IgA1的β1、3Gal-T不可缺少的C1GALT1C1表达水平。
结果:与健康对照组相比,IgAN患者的Gd-IgA1水平显着更高。与健康对照组相比,IgAN患者中C1GALT1基因的表达水平显着下调。 C1GALT1的mRNA水平与Gd-IgA1水平呈负相关。在荟萃分析中,符合纳入标准的6篇文章(包括316名参与者)分析了β1、3Gal-T的表达。与对照组相比,IgAN患者之间C1GALT1的表达没有显着差异。而且我们发现,与对照组相比,IgAN患者的B细胞中C1GALT1基因表达水平较低。 IgAN患者的C1GALT1C1水平与对照组无差异,无论根据不同的种族,不同的对照组和不同的细胞来源,C1GALT1C1水平均无变化。包括46人在内的两项研究比较了B细胞中β1、3Gal-T的酶活性,结果表明B细胞中β1、3Gal-T的酶活性降低。
结论:我们发现,IgAN患者中C1GALT1的表达水平显着下调,并且与Gd-IgA1的较高水平呈负相关。随后的荟萃分析验证了IgAN患者B细胞中β1、3Gal-T的低表达和活性。然而,在IgAN和对照组之间在C1GALT1C1表达方面没有明显的差异。

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