新疆维、哈、汉民族SLC2A9基因功能区突变与痛风的关联研究和功能验证

目前认为痛风主要与尿酸转运蛋白变异或表达异常导致尿酸重吸收增加和排泄减少有关，确切机制尚未阐明。葡萄糖易化转运蛋白-9（SLC2A9) 主要分布于肾脏近曲小管上皮细胞的基底外膜，与尿酸重吸收密切相关。本课题组首次发现新疆不同民族尿酸水平、高尿酸血症、痛风发病率存在差异，该基因启动子区SNPs小样本筛查也存在民族差异，差异是否与该基因功能区突变导致基因转录和蛋白表达异常有关有待查明。本研究拟利用SNaPshot方法检测不同民族痛风患者和对照人群SLC2A9基因功能区SNPs和tag SNPs，采用定点突变技术及双荧光素酶报告基因系统检测阳性SNPs位点对基因转录水平的影响，荧光定量PCR和Western Blot方法检测痛风患者肾活检组织和尿沉渣中脱落的肾小管上皮细胞中SLC2A9蛋白表达水平，从功能研究的角度探讨痛风发病分子机制及民族异质性的深层次机理，为不同民族痛风特异性防治提供新的靶点。

Uric acid transporter protein mutation or abnormal expression can leads to uric acid reabsorption and excretion disorder, this maybe the mainly reason for hyperuricemia and gout.But the exact mechanism has not been elucidated. Facilitated glucose transporter protein-9 (SLC2A9) located in the renal proximal tubule epithelial cell basolateral membrane, plays an important role in the process of reabsorption of uric acid. Our research team first discovered the uric acid levels, incidence of hyperuricemia and gout were difference in different ethnic. We still found SLC2A9 gene promoter region SNPs were different too in these ethnic, the genetic mechanisms must be verified. So this study intends to detect SLC2A9 gene promoter region SNPs and tag SNPs use SNaPshot method in gout and countrol group of Han,Uygur and Hazarker nations firstly, then using site-directed mutagenesis and dual luciferase reporter gene system to detect the relationship between SNPs and gene transcription. Finally, apply RT-PCR and Western Blot technology to detect SLC2A9 protein levels of renal tubular epithelial cells in patients with gout from Renal biopsy and urine sediment sample. The aim is want to found the molecular pathogenesis mechanism of gout and ethnic heterogeneity from a gene funtion new perspective, give a new drug targets specific for treatment and prevention to different nations gout patient in future.