Single nucleotide polymorphism (SNP) in COX-2 promoter gene:roles in the prevention of overactive bladder caused by cerebro-vascular accident or bladder outlet obstruction

据报道，COX-2启动子的一个新的变异体-765(-765G-&gt；C)鸟嘌呤到胞嘧啶的取代位于转录因子SPL的一个可能的结合部位。研究发现，COX-2基因的多态与降低心肌梗死和中风的风险有关，这与PGE2的产生减少有关。以前我们曾报道PGE2在大脑和脊髓的神经元可塑性中发挥重要作用，这导致了OAB的发展。因此，在BPH或卒中患者中，携带-765GC或-765CC基因的患者，OAR的发展被认为是减少的。本研究根据国际前列腺症状评分(IPSS/OAB)将脑血管意外、脊髓损伤或膀胱出口梗阻(BOO)患者分为两组：膀胱过度活动组(OAB)和非过度活动组(Non-OAB)。所有患者的血样和尿样均采集。…法制备宝石DNA用限制性内切酶消化聚合酶链式反应产物，对更多的D和-765G-&gt；C变异进行基因分型。进行基因分型。分析尿前列腺素E_2(PGE_2)水平与OAB严重程度的关系。2006年和2007年的研究结果如下：1.BOO患者尿PGE_2水平明显高于对照组。脑血管意外患者尿PGE2水平与IPSS严重程度相关。IPSS评分高的患者尿PGE2.3水平也高。环氧合酶抑制剂剂量依赖地抑制大鼠脑梗塞引起的逼尿肌过度活动。这种作用依赖于对膀胱内C-5传入神经的抑制。70例OAB患者中有3例COX-2启动子基因存在单核苷酸多态性。结果将在东京举行的2008年国家统计局年会上公布。我们必须积累样本来分析SNP与OAB严重程度的相关性。PGE2在膀胱扩张时从尿路上皮分泌出来，刺激C-5传入神经，从而促进逼尿肌过度活动。这一机制似乎适用于BOO患者。而脑血管意外患者血清PGE2水平与OAB的严重程度相关。他们并没有被证明存在，阿布。这些结果表明，可能存在其他潜在的机制来解释PGE2在OAB中的作用。较少

It has been reported that a new variant in the COX-2 promoter, a guanine to cytosine substitution at -765 (-765G->C) is located within a putative binding site for the transcription factor Spl. The polymorphism of the COX-2 gene was found to associate with a decreased risk of myocardial infarction and stroke by reduction in PGE2 production. Previously we reported that PGE2 played an important role in neuron-plasticity in the brain and spine, which resulted in the development of OAB. Therefore, in BPH or stroke patients with -765GC genotype or -765CC genotype, development of OAR in believed to be diminished. In the present study, the patients with cerebrovascular accident, spinal lesion, or bladder outlet obstruction (BOO) were classified into two groups ; overactive bladder (OAB) group and non-overactive bladder (non-OAB) group according to the International Prostate symptom Score (IPSS)/OAB symptom score. Blood and urine samples were collected from all patients. Gemonic DNA was prepare … More d from blood and -765G->C variant was genotyped by restriction endonuclease digestion of the polymerase chain reaction product. Genotypes were determined. The level of prostaglandin E2 (PGE2) in the urine were analyzed with the severity of OAB. The results obtained in 2006 and 2007 were as follows;1. The urine levels of PGE2 in patients with BOO were significantly higher than that in control.2. The urine level of PGE2 in patients with cerebrovascular accident was correlated with severity of IPSS. The patients with high score of IPSS reveals high level of urine PGE2.3. COX inhibitors dose-dependently inhibited detrusor overactivity caused by cerebral infarction in rats. This effect was dependent on suppression of C-fiver afferent nerves in the bladder.4. Single nucleotide polymorphism (SNP) in COX-2 promoter gene was found in 3 out of 70 patients with OAB. The results will be presented at 2008 NBS annual meeting in Tokyo. We have to accumulate the samples to analyze the correlation between SNP and severity of OAB.PGE2 excreted from the urothelium in response to bladder distension stimulates C-fiver afferent nerves, subsequently promoting detrusor overactivity. This mechanism seems to be true in patients with BOO. However, the levels of PGE2 were related with the severity of OAB in patients with cerebrovascular accidents. They were not proven to exist BOO. These results suggest that there might exist other underlying mechanisms to explain the role of PGE2 in OAB. Less