Department of Nephrology, General Hospital of Tianjin Medical University, Anshan road, Heping district, Tianjin, 154, NO, China.
BMC Nephrol. 2020 Jan 15;21(1):18. doi: 10.1186/s12882-019-1675-5.
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.
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.
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.
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.
越来越多的研究表明,C1GALT1 中的遗传变异会影响 IgAN 中的 Gd-IgA1 水平。然而,β1,3-半乳糖基转移酶(β1,3Gal-T)的表达是否受到影响可能有助于了解 IgAN 中 Gd-IgA1 水平是如何受到控制的。
本研究纳入了 2018 年 4 月至 9 月在天津医科大学总医院诊断为 IgAN 的 30 例患者和年龄、性别与之匹配的 30 名健康志愿者。采用 ELISA 法测定血浆总 Gd-IgA1 水平,采用 RT-PCR 法测定 C1GALT1 水平。检索了 PubMed、EMBASE、中国知网(CNKI)和万方医学网(WanFang Medical Network)4 个数据库,以确定评估 IgAN 患者与总对照组(非 IgAN 和健康对照组)之间 C1GALT1 表达差异的合格研究。还比较了 IgA1 中不可或缺的β1,3Gal-T 的 C1GALT1C1 表达水平。
IgAN 患者的 Gd-IgA1 水平明显高于健康对照组。IgAN 患者的 C1GALT1 基因表达水平明显低于健康对照组。并且 C1GALT1 的 mRNA 水平与 Gd-IgA1 水平呈负相关。荟萃分析纳入了 6 项包含 316 名参与者的分析β1,3Gal-T 表达的研究。IgAN 患者与对照组之间 C1GALT1 的表达无显著差异。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人群、不同的对照组还是不同的细胞来源,C1GALT1C1 水平均保持不变。两项包含 46 人的研究比较了 B 细胞中β1,3Gal-T 的酶活性,结果显示 B 细胞中的β1,3Gal-T 活性降低。
我们发现 IgAN 患者的 C1GALT1 表达水平明显下调,与 Gd-IgA1 水平升高呈负相关。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,IgAN 组与对照组在 C1GALT1C1 表达方面无明显差异。