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

我们采用人血和动物病理模型，探讨代谢综合征相关基因多态性与下尿路症状发生的关系。器官缺血被认为是由金属蛋白酶（MMPs）消化基质导致动脉粥样硬化斑块破裂引起的。巨噬细胞MMP-2和MMP-9的产生是由环氧化酶-2 （COX-2）和前列腺素E2 （PGE2）合成诱导的。COX-2基因的the - 765g ->C多态性已被报道与心肌梗死和中风风险降低相关。由于膀胱缺血被认为是下尿路症状（CUTS）的重要风险之一，因此检测该基因型可能有助于预测膀胱储存功能障碍的遗传风险。利用膀胱过动症（OAB）患者的血液样本，对765g ->变异进行基因分型。由于该变异在这些患者中的患病率较低，因此未发现显著相关性。接下来，为了进一步研究尿中PGE2、PGF2α、神经生长因子（NGF）和P物质水平与OAB症状之间的关系，我们采用酶联免疫吸附法分析了114名脑部疾病慢性期患者和27名健康对照者的尿液样本。因此，推测尿PGE2水平在高钠质脑病患者中升高，并与OAB的存在相关。我们收集了在日本福井参加多阶段健康筛查的28,238人（9,286名男性和18,952名女性）的数据。夜尿症（定义为每晚两次或两次以上排空）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、BMI<18.5、BMI>27.0、高血压和糖耐量受损。代谢产物的组成与夜尿有关。我们利用脑梗死大鼠动物模型，探讨脑高钠质疾病患者尿PGE2水平升高的潜在机制。CI大鼠膀胱内ATP含量为假手术大鼠（SO）的2.24倍。与SO大鼠比较，CI后膀胱壁P2X3、ASIC2、TRPV1、M2、M3 mRNA表达增加，提示膀胱C纤维传入神经表达上调。这些变化在树脂干扰素预处理的大鼠中没有发现。作为代谢综合征的动物模型，我们给大鼠喂食富含果糖的食物11个月。大鼠表现为高血压、葡萄糖耐受不良和频繁排尿。大鼠膀胱壁COX-2表达增加。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