東京大學醫(yī)學部附屬醫(yī)院準教授野入英世等人的研究小組近日宣布,，他們發(fā)現(xiàn)了與腎病癥候群相關(guān)的新的遺傳基因,。
研究小組經(jīng)過對該遺傳基因進行詳細的機能分析,，發(fā)現(xiàn)該遺傳基因與維持排尿時過濾血液中廢棄成分的腎臟過濾結(jié)構(gòu)有關(guān),。該遺傳基因在受到有害刺激時，容易破壞腎臟過濾結(jié)構(gòu),，出現(xiàn)腎病癥候群主要癥狀,，即尿中有高蛋白的現(xiàn)象。研究小組在實驗中通過阻礙該遺傳基因,，發(fā)現(xiàn)腎臟過濾結(jié)構(gòu)脆弱性消失，防止了蛋白尿的出現(xiàn),。在糖尿病發(fā)病后,，采用阻礙該遺傳基因的藥物治療，蛋白尿也會減少,。
腎病癥候群是由于腎小球異常，排出的尿中有大量蛋白，從而導致血中蛋白異常低下,，引起低蛋白血癥的腎病的總稱,。腎病癥候群有原發(fā)性和糖尿病導致的二次性兩種類型,，能夠引起全身各個器官疾病發(fā)生。究其成因,，科學家在此之前，僅發(fā)現(xiàn)了與家族性腎病癥候群相關(guān)的多個遺傳基因和一基因多型,，但對腎病癥候群全體共通的病態(tài)機理尚未了解,。因此，對該病的治療只能使用副作用極強的腎上腺皮質(zhì)激素和免疫抑制藥物,，沒有根本的治療方法。
而新的研究成果可望用于開發(fā)診斷,、治療和預防腎病癥候群的有效方法,。
相關(guān)論文將刊載在最近出版的英國《自然—遺傳學》雜志上,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
