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尿路結石のオステオポンチン一塩基多型(SNP)の機能解析と遺伝子診断法の開発

尿路结石中骨桥蛋白单核苷酸多态性（SNP）的功能分析及遗传诊断方法的开发

基本信息

批准号：
18791132
负责人：
安井孝周
金额：
$ 2.24万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18791132/
关键词：
遺伝子診断一塩基多型オステオポンチン転写活性塩基多型

项目摘要

本研究は結石マトリクス,オステオポンチン(OPN)の一塩基多型(SNPs)の機能解析を行い,結石形成への影響を調べることを目的とした。健常者と結石患者から血液を採取し,DNA sequenceと5'nuclease assay (TaqMan Assay)でSNPsを解析した。61ヶ所のSNPsを確認し,4つのhtSNPsについて,結石患者および健常者に特異的なハプロタイプを同定した。ハプロタイプ(G-T-T-G)は結石患者に多く(p=0.0227 odds比1.676),ハプロタイプ(T-G-T-G)は健常者に多く(p=0.016 odds比0.351)みられた。結石患者と健常人に特徴的なhaplotypeをもったOPNプロモーター領域を-4500bpまで含んだ遺伝子配列を作成し,プロモーター活性検査用ベクターに組み込んだ。尿細管細胞(NRK-52E)に遺伝子導入し,Luciferase assayにて結石形成時に起こると考えられる蓚酸負荷(0.5〜2mM蓚酸ナトリウム)および蓚酸カルシウム(COM)結晶の添加を行った際の転写活性を検討した。蓚酸およびCOM結晶の刺激により,OPNプロモーター活性は経時的に上昇したが,ハプロタイプ(T-G-T-G)はハプロタイプ(G-T-T-G)と比較して有意に上昇していた。OPNのハプロタイプ(G-T-T-G)は結石発症のリスクが高く,ハプロタイプ(G-T-T-G)は低いと考えられた。本研究の結果は採血による遺伝子解析が結石発症リスクの予想を可能にすることが示唆された。

The results of this study show that OPN can analyze the performance of multiple models (SNPs), and the results show that there are significant differences between the two groups. In normal patients, blood samples were collected from normal patients, and DNA sequence 5'nuclease assay (TaqMan Assay) SNPs were analyzed. 61 the SNPs was confirmed, and the htSNPs was confirmed in 4 months. The results showed that the patients had the same diagnosis as the normal ones. The number of patients with chronic hepatitis B (G-T-T-G) was higher than that of normal subjects (0.0227 odds vs 1.676), and that of normal patients (T-G-T-G) was 0.016 odds than 0.351. Results the domain of the patient's "haplotype" and "OPN" of the patient's "normal person" was made up of the sub-array of the 4500bp gene containing the drug, and the activity of the drug was measured by the enzyme assay. The urinary trachea cell (NRK-52E) was inserted into the urine, and the Luciferase assay test started at the time of the formation of the 0.5~2mM. Acid loading (0.5~2mM), acid loading (COM), acid cycle (COM), acid loading, and writing activity. The COM results show that it is necessary to stimulate the activity of the OPN, and that the T-G-T-G is not active. The G-T-T-G is intended to be activated. The OPN syndrome (G-T-T-G) results showed that the symptoms were high, while the G-T-T-G was low. The results of this study showed that the blood samples were analyzed and the symptoms were predicted that they might show signs of instigation.