Sun Weiping, Yao Sihong, Tang Jielong, Liu Shuai, Chen Juan, Deng Daqing, Zeng Chunping
Department of Geriatrics, the First People's Hospital of Xiangtan City, Xiangtan, PR, China.
Department of Clinical Medicine, Jishou University School of Medicine, Jishou, PR, China.
PLoS One. 2018 Jan 31;13(1):e0192105. doi: 10.1371/journal.pone.0192105. eCollection 2018.
Clinical studies in type 2 diabetes (T2D) primarily focused on the single nucleotide polymorphisms (SNPs) located in protein-coding regions. Recently, the SNPs located in noncoding regions have also been recognized to play an important role in disease susceptibility. The super enhancer is a cluster of transcriptional enhancers located in noncoding regions. It plays a critical role in cell-type specific gene expression. However, the exact mechanism of the super enhancer SNPs for T2D remains unclear. In this study, we integrated genome-wide association studies (GWASs) and T2D cell/tissue-specific histone modification ChIP-seq data to identify T2D-associated SNPs in super enhancer, followed by comprehensive bioinformatics analyses to further explore the functional importance of these SNPs. We identified several interesting T2D super enhancer SNPs. Interesting, most of them were clustered within the same or neighboring super enhancers. A number of SNPs are involved in chromatin interactive regulation and/or potentially influence the binding affinity of transcription factors. Gene Ontology (GO) analysis showed a significant enrichment in several well-known signaling pathways and regulatory process, e.g. WNT signaling pathway, which plays a key role in T2D metabolism. Our results highlighted the potential functional importance of T2D super enhancer SNPs, which may yield novel insights into the pathogenesis of T2D.
2型糖尿病（T2D）的临床研究主要集中在位于蛋白质编码区的单核苷酸多态性（SNP）上。最近，位于非编码区的SNP也被认为在疾病易感性中起重要作用。超级增强子是位于非编码区的一组转录增强子。它在细胞类型特异性基因表达中起关键作用。然而，超级增强子SNP导致T2D的确切机制仍不清楚。在本研究中，我们整合了全基因组关联研究（GWAS）和T2D细胞/组织特异性组蛋白修饰ChIP-seq数据，以鉴定超级增强子中与T2D相关的SNP，随后进行全面的生物信息学分析，以进一步探索这些SNP的功能重要性。我们鉴定了几个有趣的T2D超级增强子SNP。有趣的是，它们中的大多数聚集在相同或相邻的超级增强子内。许多SNP参与染色质相互作用调节和/或可能影响转录因子的结合亲和力。基因本体（GO）分析显示在几个著名的信号通路和调节过程中显著富集，例如在T2D代谢中起关键作用的WNT信号通路。我们的结果突出了T2D超级增强子SNP的潜在功能重要性，这可能为T2D的发病机制提供新的见解。
