Does polymorphism of metabolic syndrome-related genes induce lower urinary tract symptoms?

代谢综合征相关基因多态性是否会诱发下尿路症状？

• 批准号: 20390422
• 负责人: YOKOYAMA Osamu
• 金额: $ 11.98万
• 依托单位: University of Fukui
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390422/
• 关键词: メタボリック症候群; 遺伝子多型; 下部尿路症状; COX-2; プロスタグランジン; 脳障害; 過活動膀胱; 夜間頻尿; 肥満; 尿

We investigated the relationship between polymorphism of metabolic syndrome-related gene and occurrence of lower urinary tract symptoms, using human blood samples and animal pathological models.Organ ischemia is thought to be caused by matrix digestion by metalloproteinases (MMPs) leading to rupture of atherosclerotic plaques. Production of macrophage MMP-2 and MMP-9 is induced by cycloxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis. The-765G->C polymorphism of the COX-2 gene has been reported to associate with a decrease risk of myocardial infarction and stroke. Detection of this genotype may be useful to predicting genetic risk of bladder storage dysfunction because bladder ischemia is known as one of the important risks for lower urinary tract symptoms (CUTS). Using blood samples of patients with overactive bladder (OAB), the-765G->Cvariant was genotyped. As the prevalence of the variant was low in these patients, the significant relationship was not found. Next, to investi … More gate the association between the urinary levels of PGE2, PGF2α, nerve growth factor (NGF) and substance P, and OAB symptoms, urine samples from 114 patients in the chronic phase of a brain disease and 27 healthy controls were analyzed by enzyme-linked immunosorbent assay. As a result, the urinary PGE2 level was putatively elevated in patients with suprapontine brain diseases and associated with the presence of OAB. We collected data on 28,238 individuals (9,286 males and 18,952 females) who participated in a multiphasic health screening in Fukui, Japan. The overall prevalence of nocturia (defined as two or more voids/night) was 5.8%. In the multivariate analysis, a significant association was found between nocturia and the followings:age, male gender, BMI<18.5, BMI>27.0, high blood pressure and impaired glucose tolerance. The number of components of MetS was correlated with nocturia.Using rat animal models with cerebral infarction (CI), we investigated the underlying mechanism of increase in the urinary PGE2 level in patients with suprapontine brain diseases. The ATP amount in the bladder of CI rats was 2.24 times larger than that of sham operated(SO) rats 6 hours after CI. Compared with SO rats, the mRNA expression of P2X3, ASIC2, TRPV1, M2 and M3 in the bladder wall increased after CI, meaning upregulation of C fiber afferent nerves of the bladder. These changes were not found in rats pretreated with resiniferatoxin.As an animal model of metabolic syndrome, rats were fed with fructose-rich diet for 11 months. Rats revealed hypertension, glucose intolerance, and frequent voiding. The expression of COX-2 in the bladder wall was found to increase in these rats. Less

我们采用人血标本和动物病理模型研究代谢综合征相关基因多态性与下尿路症状发生的关系，认为器官缺血是由基质金属蛋白酶（MMPs）消化基质导致动脉粥样硬化斑块破裂所致。巨噬细胞MMP-2和MMP-9的产生由环氧化酶-2（考克斯-2）和前列腺素E2（PGE 2）的合成诱导。考克斯-2基因的-765 G->C多态性与心肌梗死和中风风险降低相关。这种基因型的检测可能有助于预测膀胱储存功能障碍的遗传风险，因为膀胱缺血被认为是下尿路症状（CUTS）的重要风险之一。使用膀胱过度活动症（OAB）患者的血液样本，对-765G-> C变体进行基因分型。由于这些患者中该变异的患病率较低，因此未发现显著相关性。 ...更多信息 采用酶联免疫吸附试验（ELISA）检测114例脑疾病慢性期患者和27例健康对照者的尿PGE 2、PGF 2 α、神经生长因子（NGF）和P物质（SP）水平。结果表明，脑桥上疾病患者尿PGE_2水平明显升高，并与OAB的存在有关。我们收集了28，238人（9，286名男性和18，952名女性）的数据，这些人参加了日本福井的多阶段健康筛查。排尿困难（定义为每晚排尿两次或两次以上）的总体患病率为5.8%。多因素分析显示，年龄、男性、BMI<18.5、BMI>27.0、高血压、糖耐量异常与糖尿病有显著相关性。采用大鼠脑梗死（cerebral infarction，CI）动物模型，探讨脑桥上脑疾病患者尿PGE 2水平升高的可能机制。CI后6 h，CI组大鼠膀胱ATP含量是SO组的2.24倍。与SO大鼠相比，CI后膀胱壁P2 X3、ASIC 2、TRPV 1、M2和M3的mRNA表达增加，提示膀胱C纤维传入神经上调。作为代谢综合征的动物模型，用富含果糖的饲料喂养大鼠11个月。大鼠表现出高血压、葡萄糖耐受不良和频繁排尿。膀胱壁考克斯-2表达增加。少

项目成果

Understanding the Science, 30th Congress of the Societe Internationale d'Urologie

了解科学，国际泌尿外科协会第 30 届大会

• 发表时间: 2009
• 作者: Kitagawa K.;Yanagisawa S.;Watanabe K.;Yunoki T.;Hayashi A.,Okabe M.;Nikaido T.;横山修
• 通讯作者: 横山修

夜間頻尿、日本人の特徴とその背景因子について

日本人的夜尿特征及其背景因素

• 发表时间: 2009
• 作者: 三輪吉司;金田大生;大山伸幸;秋野裕信;横山修;公文裕巳;Suzuki A;横山修
• 通讯作者: 横山修

Neurogenic Bladder Society Clinical guidelines for overactive bladder.

神经源性膀胱协会膀胱过度活动症的临床指南。

• 发表时间: 2009
• 期刊: Int J Urol 16
• 作者: Yamaguchi O;Nishizawa O;Takeda M;Yokoyama O;Homma Y;Kakizaki H;Obara K;Gotoh M;Igawa Y;Seki N;Yoshida M
• 通讯作者: Yoshida M

Relationship between nocturia and metabolic syndrome

夜尿与代谢综合征的关系

• 发表时间: 2009
• 作者: Aoki Y;Kusukawa N;Matsuta Y;Maegawa M;Tanase K;Ito H;Oyama N;Miwa Y;Akino H;Yokoyama O
• 通讯作者: Yokoyama O

Association Between Lower Urinary Tract Symptoms and Serum Levels of Sex Hormones in Men

男性下尿路症状与血清性激素水平之间的关联

• 发表时间: 2008
• 期刊: Urology 72
• 作者: Yoshiji Miwa;Taisei Kaneda;Osamu Yokoyama
• 通讯作者: Osamu Yokoyama