Department of Nutrition and Food Technology, Jashore University of Science and Technology, Jashore, Bangladesh.
Department of Immunology, Health Science Center, Shenzhen University, Shenzhen, China.
PLoS One. 2022 Aug 29;17(8):e0268826. doi: 10.1371/journal.pone.0268826. eCollection 2022.
Type 2 diabetes (T2D) has earned widespread recognition as a primary cause of death, disability, and increasing healthcare costs. There is compelling evidence that hereditary factors contribute to the development of T2D. Clinical trials in T2D have mostly focused on genes and single nucleotide polymorphisms (SNPs) in protein-coding areas. Recently, it was revealed that SNPs located in noncoding areas also play a significant impact on disease vulnerability. It is required for cell type-specific gene expression. However, the precise mechanism by which T2D risk genes and SNPs work remains unknown. We integrated risk genes and SNPs from genome-wide association studies (GWASs) and performed comprehensive bioinformatics analyses to further investigate the functional significance of these genes and SNPs. We identified four intriguing transcription factors (TFs) associated with T2D. The analysis revealed that the SNPs are engaged in chromatin interaction regulation and/or may have an effect on TF binding affinity. The Gene Ontology (GO) study revealed high enrichment in a number of well-characterized signaling pathways and regulatory processes, including the STAT3 and JAK signaling pathways, which are both involved in T2D metabolism. Additionally, a detailed KEGG pathway analysis identified two major T2D genes and their prospective therapeutic targets. Our findings underscored the potential functional significance of T2D risk genes and SNPs, which may provide unique insights into the disease's pathophysiology.
2 型糖尿病（T2D）已被广泛认为是导致死亡、残疾和医疗保健费用不断增加的主要原因之一。有确凿的证据表明遗传因素导致了 T2D 的发生。T2D 的临床试验主要集中在蛋白质编码区域的基因和单核苷酸多态性（SNPs）上。最近，研究发现位于非编码区域的 SNPs 也对疾病易感性产生重大影响。它是细胞类型特异性基因表达所必需的。然而，T2D 风险基因和 SNPs 的作用机制仍不清楚。我们整合了来自全基因组关联研究（GWAS）的风险基因和 SNPs，并进行了全面的生物信息学分析，以进一步研究这些基因和 SNPs 的功能意义。我们确定了四个与 T2D 相关的有趣转录因子（TFs）。分析表明，这些 SNPs 参与了染色质相互作用的调节，或者可能对 TF 结合亲和力产生影响。基因本体论（GO）研究揭示了许多特征明确的信号通路和调控过程的高度富集，包括 STAT3 和 JAK 信号通路，它们都参与了 T2D 的代谢。此外，详细的 KEGG 途径分析确定了两个主要的 T2D 基因及其潜在的治疗靶点。我们的研究结果强调了 T2D 风险基因和 SNPs 的潜在功能意义，这可能为该疾病的病理生理学提供独特的见解。
