ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2014, Vol. 23 ›› Issue (1): 6-12.

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汉族和高加索人糖尿病肾病肾小球全基因组表达数据分析

  

  • 出版日期:2014-02-28 发布日期:2014-02-25

Comparison of the glomerular whole-genome scale gene expression profile between Chinese Han and Caucasian patients with diabetic nephropathy

  • Online:2014-02-28 Published:2014-02-25

摘要:

摘 要 目的:观察中国汉族人群和高加索人群间糖尿病肾病患者肾小球内差异表达基因和发生调节的分子信号通路的异同。方法:我们分别选取中国汉族人群糖尿病肾病患者29例和正常对照5例,及高加索人群糖尿病肾病患者21例及正常对照35例,微分离肾小球进行全基因组表达数据检测,分析不同人种中糖尿病肾病患者同正常对照相比出现差异表达的基因;分析不同人种糖尿病肾病患者肾小球内及同eGFR变化相关的表达基因;比较差异表达基因及同eGFR变化相关基因在中国汉族人群和高加索人群中的异同。结果:(1)在中国汉族人群糖尿病肾病患者的肾小球中有565个基因存在差异表达,在高加索人群糖尿病肾病患者肾小球中有775个基因存在差异表达;(2)比较分析提示,有200个基因在不同人种中均村子啊差异表达。分子通路分析提示,共有13条信号通路在不同人种中均发生调节,其中大部分为免疫炎症反应相关性通路;(3)在中国汉族人群中有225个基因同eGFR明显相关;而在高加索人群中,有293个基因同eGFR明显相关。比较分析提示,共有CRISPLD2、SPON1、LUM等55个基因在不同人种中同时与eGFR水平明显相关。结论:通过比较分析中国汉族人群和高加索人群糖尿病肾病患者肾小球全基因组表达谱的异同,发现免疫炎症通路在不同人种糖尿病肾病的发生发展中均发挥重要作用。于此同时,我们还获得了55个与不同人种糖尿病肾病患者肾功能改变明显相关的基因,这些基因可以作为判断糖尿病肾病患者疾病进展分子标志物的候选基因进行研究验证。

关键词:  糖尿病肾病, 全基因组表达谱, 发病机制, 炎症

Abstract:

ABSTRACT Objective:To investigate the common and different regulated genes and their molecular pathways between diabetic nephropathy (DN) patients in Chinese Han and Caucasian population. Methodology:Twenty nine Chinese Han DN patients and 6 normal control, 21 Caucasian DN patients and 35 normal control were selected in this study. The glomeruli were micro-dissected. The Affymetrix human U133 plus 2.0 chip were used to detect the whole-genome scale gene expression profile of the glomeruli. The regulated genes between DN and normal control and the genes associated with the eGFR of DN patients had separately been analyzed. Then, the common and different regulated genes and genes associated with eGFR of DN between Chinese Han and Caucasian population was compared to used comparative analysis . Results:(1) 565 genes were regulated in the Chinese Han DN patients compared with the normal control, while 775 genes were regulated in the Caucasian DN patients compared with their normal control. (2) Comparative analysis showed that 200 genes were both regulated in the Chinese Han and Caucasian DN patients, and the regulated directions were same. Enriched pathway analysis revealed 13 signaling pathways were both regulated in the Chinese Han and Caucasian DN patients. Most of the regulated signaling pathways were involved in the inflammation response. (3) 225 genes and 293 genes associated with eGFR in Chinese Han and Caucasian DN patients, respectively. Comparative analysis showed that 55 genes including CRISPLD2、SPON1、LUM and so on were significantly associated with eGFR in both two races. Conclusion:We revealed a series of genes and pathways which were both regulated in Chinese Han and Caucasian DN patients, and found that the inflammation pathways play critical role in the progression of DN in both races. We also demonstrated that 55 genes were associated with the changes of renal function in both Chinese Han and Caucasian DN patients. These genes had the potential to be the prognostic biomarkers of DN patients, but it still need to be validated in the further study.

Key words: diabetic nephropathy, whole-genome scale gene expression profile, molecular mechanisms, inflammation