前列腺癌有多个SNP变异被GWAS研究报道，然而对于它们的生物机制却十分缺乏了解。我们前期研究发现，当rs339331（GPRC6a/RFX6）碱基为"T"时，GPRC6a及RFX6的表达明显较为"A"时增高。骨钙素是GPRC6a的激动剂之一，病例分析发现骨钙素与前列腺癌的发展转移存在剂量效应。据此我们假设，GPRC6a/RFX6基因区域SNPs可能影响GPRC6a等基因的功能，从而影响前列腺癌的发生发展，且可能参与骨钙素-leydig细胞-雄激素-前列腺癌调控。我们拟通过Chip，3C，NOMe-Seq, hMedip/Medip等技术对该区域DNA立体构象、转录因子结合能力、核小体定位及表观遗传学修饰等进行检测，探索此区域SNP的功能，然后进行体外（细胞）及体内（基因打靶小鼠）功能验证，最终阐明GPRC6a/RFX6基因区域SNPs在前列腺癌发生发展中的生物机制。

More than 60 independent susceptibility loci have been identified by genome-wide association studies (GWAS). However, the mechanistic roles of these SNPs remain poorly defined. In previously research we observe a significant association between the risk-associated T allele at rs339331(GPRC6a/RFX6) and increased RFX6 and GPRC6a mRNA levels in human prostate tumors, because osteocalcin are one of agonists of GPRC6a, then we found that osteocalcin did play a role in proliferation, migration and invasion of PCa. In order to assess the effects of genetic variations on GPRC6a, this project is proposed to apply Chip，3C, NOMe-Seq , hMedip/ Medip technology on PCa cells or PCa tissue . The roles of genetic variations in the development of PCa will be revealed through the analysis of transcription binding，chromosome comformation,nucleosome positioning and epigenetic modification. Clarifying the function of the GPRC6a variants and their link to ostocalcin regulation will allow a deeper understanding of the mechanisms underlying human cancer development.