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

我们利用人类血液样本和动物病理模型，研究了代谢综合征相关基因多态性与下尿路症状发生的关系。器官缺血被认为是金属蛋白酶(MMPs)对基质的消化，导致动脉粥样硬化斑块破裂。巨噬细胞产生的基质金属蛋白酶-2和基质金属蛋白酶-9是由环氧合酶-2(COX-2)和前列腺素E2(PGE2)的合成诱导的。据报道，COX-2基因的-765G-&GT；C多态与降低心肌梗死和中风的风险有关。检测该基因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(CUT)的重要风险之一。利用膀胱过度活动症(OAB)患者的血液样本，对-765G-&gt；变异体进行了基因分型。由于该变异在这些患者中的患病率很低，因此没有发现显著的相关性。接下来，要投资…进一步探讨尿前列腺素E_2、前列腺素F_2α、神经生长因子和P物质水平与OAB症状的关系。用双抗体夹心酶联免疫吸附试验对114例脑部疾病慢性期患者和27例健康人的尿液进行分析。因此，桥上脑疾病患者的尿PGE2水平可能升高，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，他们参加了日本福井的一项多阶段健康筛查。夜尿症(定义为每晚排尿两次或以上)的总体患病率为5.8%。在多变量分析中，夜尿症与以下因素显著相关：年龄、男性、体重指数18.5、体重指数27.0、高血压和糖耐量减退。利用大鼠脑梗塞(CI)动物模型，研究桥上脑疾病患者尿PGE2水平升高的可能机制。脑梗塞后6h，脑梗死组大鼠膀胱内的三磷酸腺苷含量是假手术组的2.24倍。与SO组比较，CI组大鼠膀胱壁P2X3、ASIC2、TRPV1、M2、M3mRNA表达增加，提示膀胱C纤维传入神经表达上调。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。大鼠表现为高血压、糖耐量低减和尿频。大鼠膀胱壁COX-2表达增强。较少

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