我们通过GWAS发现GRK5-rs1088647是一个新的2型糖尿病遗传易感位点，但是其作用机制尚不清楚。本项目将通过生物信息学的方法和一些公共数据库的数据，筛选出该基因区域的潜在功能性SNP位点（位于增强子序列内的转录因子结合位点或者甲基化位点上），然后采用"基因特异性的基因表达分析"和"基因特异性的DNA甲基化分析"等研究手段分析从这些潜在的功能性SNP位点中筛选出真正影响基因表达的功能性位点。最后采用报告基因分析和EMSA等实验手段在3T3-L1前脂肪细胞系内进行验证研究，并分析这些SNP位点是否会影响特点转录因子结合位点与转录因子的结合能力。该项目的研究不仅可以阐明GRK5-rs10886671位点影响基因转录表达的机制，而且也将为证明GRK5是一个2型糖尿病基因提供更为直接的证据。

e identified GRK5-rs10886471 as a novel type 2 diabetes locus, which confers type 2 diabetes risk by altering expression of GRK5 gene, and subsequently deceasing insulin sensitivity. However, mechanism by which RK5-rs10886471 affects gene expression remains unknown. In this study, the SNP with potential cis-regulatory function will be selected through fine mapping and searching into public databases including ENCODE and Roadmap. From which a functional cis-regulatory variant will be identified by further performing allele-specific gene expression analysis and allele-specific DNA methylation analysis in human adipose tissues. All findings in human adipose tissue will be validated in 3T3-L1 preadipocyte cell line using luciferase reporter gene assay and EMSA assay. The results of this study will not only clarify mechanism by which GRK5-rs10886471 affect expression of GRK5 gene, but also provide direct evidence that GRK5 is a type 2 diabetes gene.