Genetic studies on familial interstitial nephritis

家族性间质性肾炎的遗传学研究

• 批准号: 21591045
• 负责人: TSUKAGUCHI Hiroyasu
• 金额: $ 3万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591045/
• 关键词: 尿細管; ゲノム; 疾患遺伝子; 慢性腎臓病; 腎不全; 間質性腎炎; 連鎖解析; 腎尿細管

Chronic kidney disease(CKD) is clinically heterogeneous groups of diseases at a higher risk of potentially progressing to the end stage renal failure. The CKD is becoming a global health problem since it is indeed highly prevalent at one in eight adult individuals. The tubule-interstitial injuries significantly contribute to the pathogenesis of CKD as a primary initiating factor and/or a secondary exacerbating changes resulting from the glomerular insults. However, earlier tubule-interstitial injuries are often under-recognized because the patients barely manifest overt proteinuria and renal dysfunction. To improve the treatment for CKD, there is a need for elucidation of new disease biomarkers and genetic risk factors underlying tubule-interstitial diseases.This study aimed to identify the disease genes underling a large dominant family with tubule-interstitial nephritis. A combined approach of linkage analysis and next generation sequencing revealed that two novel single nucleotide variants may explain the susceptibility for interstitial nephritis.

慢性肾脏病（CKD）是临床异质性疾病，可能进展为终末期肾衰竭的风险较高。CKD正在成为一个全球性的健康问题，因为它确实在八分之一的成年人中非常普遍。肾小管间质损伤作为肾小球损伤的主要始动因素和/或继发性加重改变，在CKD的发病机制中起重要作用。然而，早期肾小管间质损伤往往认识不足，因为患者几乎没有明显的蛋白尿和肾功能不全。为了改善慢性肾脏病的治疗，有必要阐明新的疾病生物标志物和肾小管间质疾病的遗传危险因素。本研究旨在确定一个显性肾小管间质性肾炎大家族的疾病基因。连锁分析和下一代测序的联合方法显示，两种新的单核苷酸变异可能解释间质性肾炎的易感性。

项目成果

Predisposition to relapsing nephrotic syndrome by a nephrin mutation that interferes with assembly of functioning microdomains

• DOI: 10.1093/hmg/ddp232
• 发表时间: 2009-08-15
• 期刊: HUMAN MOLECULAR GENETICS
• 影响因子: 3.5
• 作者: Shono, Akemi;Tsukaguchi, Hiroyasu;Iijima, Kazumoto
• 通讯作者: Iijima, Kazumoto

腎臓症候群第2版上V.先天性遺伝性疾患(分担執筆)

肾综合征第二版五、先天性遗传病（合着）

• 发表时间: 2012
• 作者: 村田哲也;村田真理子;塚口裕康
• 通讯作者: 塚口裕康

Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.

• DOI: 10.1038/ng.505
• 发表时间: 2010-01
• 期刊: Nature genetics
• 影响因子: 30.8

Molecular Genetics of Steroid-Resistant Nephrotic Syndromes

类固醇抵抗性肾病综合征的分子遗传学

• 发表时间: 2012
• 作者: Koda;A.;Tomita;K.;Kitamura;K.;et al;Sekine M;Hiroyasu Tsukaguchi
• 通讯作者: Hiroyasu Tsukaguchi

ネフローゼ症候群疾患遺伝子研究の最近の知見-ポドサイト遺伝子変異の重要

肾病综合征疾病遗传学研究最新发现——足细胞基因突变的重要性

• 发表时间: 2009
• 作者: 佐藤稔;他;塚口裕康
• 通讯作者: 塚口裕康