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Nature Genetics:日发现肾病症候群新风险基因

来源:科技日报 2011-04-06 14:07

东京大学医学部附属医院准教授野入英世等人的研究小组近日宣布,他们发现了与肾病症候群相关的新的遗传基因。

研究小组经过对该遗传基因进行详细的机能分析,发现该遗传基因与维持排尿时过滤血液中废弃成分的肾脏过滤结构有关。该遗传基因在受到有害刺激时,容易破坏肾脏过滤结构,出现肾病症候群主要症状,即尿中有高蛋白的现象。研究小组在实验中通过阻碍该遗传基因,发现肾脏过滤结构脆弱性消失,防止了蛋白尿的出现。在糖尿病发病后,采用阻碍该遗传基因的药物治疗,蛋白尿也会减少。

肾病症候群是由于肾小球异常,排出的尿中有大量蛋白,从而导致血中蛋白异常低下,引起低蛋白血症的肾病的总称。肾病症候群有原发性和糖尿病导致的二次性两种类型,能够引起全身各个器官疾病发生。究其成因,科学家在此之前,仅发现了与家族性肾病症候群相关的多个遗传基因和一基因多型,但对肾病症候群全体共通的病态机理尚未了解。因此,对该病的治疗只能使用副作用极强的肾上腺皮质激素和免疫抑制药物,没有根本的治疗方法。

而新的研究成果可望用于开发诊断、治疗和预防肾病症候群的有效方法。

相关论文将刊载在最近出版的英国《自然—遗传学》杂志上。(生物谷Bioon.com)

生物谷推荐原文出处:

Nature Genetics   doi:10.1038/ng.792

Common variation in GPC5 is associated with acquired nephrotic syndrome

Koji Okamoto,1, 2 Katsushi Tokunaga,2 Kent Doi,1 Toshiro Fujita,1 Hodaka Suzuki,3 Tetsuo Katoh,3 Tsuyoshi Watanabe,3 Nao Nishida,2 Akihiko Mabuchi,2 Atsushi Takahashi,4 Michiaki Kubo,5 Shiro Maeda,6 Yusuke Nakamura7 & Eisei Noiri1, 8

Severe proteinuria is a defining factor of nephrotic syndrome irrespective of the etiology. Investigation of congenital nephrotic syndrome has shown that dysfunction of glomerular epithelial cells (podocytes) plays a crucial role in this disease1. Acquired nephrotic syndrome is also assumed to be associated with podocyte injury. Here we identify an association between variants in GPC5, encoding glypican-5, and acquired nephrotic syndrome through a genome-wide association study and replication analysis (P value under a recessive model (Prec) = 6.0 × 10?11, odds ratio = 2.54). We show that GPC5 is expressed in podocytes and that the risk genotype is associated with higher expression. We further show that podocyte-specific knockdown and systemic short interfering RNA injection confers resistance to podocyte injury in mouse models of nephrosis. This study identifies GPC5 as a new susceptibility gene for nephrotic syndrome and implicates GPC5 as a promising therapeutic target for reducing podocyte vulnerability in glomerular disease.

 

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