The genetic regulation of the gastric transcriptome is associated with metabolic and obesity-related traits and diseases

Tissue-specific gene expression and gene regulation lead to a better understanding of tissue-specific physiology and pathophysiology. We analyzed the transcriptome and genetic regulatory profiles of two distinct gastric sites, corpus and antrum, to identify tissue-specific gene expression and its regulation. The transcriptome data from corpus and antral mucosa highlights the heterogeneity of gene expression in the stomach. We identified enriched pathways revealing distinct and common physiological processes in gastric corpus and antrum. Physiological differences are mostly related to digestion and epithelial protection. Furthermore, we found an enrichment of the single nucleotide polymorphism (SNP)-based heritability of metabolic, obesity-related, and cardiovascular traits and diseases by considering corpus- and antrum-specifically expressed genes. In particular, we could prioritize gastric-specific candidate genes for multiple metabolic traits, like NQO1 which is involved in glucose metabolism, MUC1 which contributes to purine and protein metabolism or RAB27B being a regulator of weight and body composition. Gastric corpus and antrum mucosa biopsies were collected during routine gastroscopies from up to 431 healthy individuals. We performed gene expression profiling of the two major gastric regions, corpus and antrum, using data obtained from RNA-seq.

组织特异性基因表达与基因调控，可为深入理解组织特异性生理与病理生理机制提供关键依据。本研究针对胃体（corpus）与胃窦（antrum）两个不同胃部区域的转录组及遗传调控特征展开分析，旨在鉴定组织特异性的基因表达模式及其调控机制。胃体与胃窦黏膜的转录组数据，清晰揭示了胃部基因表达的异质性。通过富集分析得到的通路信息，我们明确了胃体与胃窦各自独有的以及共有的生理过程；二者的生理差异主要与消化功能及上皮保护机制密切相关。此外，通过整合胃体与胃窦特异性表达的基因，我们发现代谢、肥胖相关及心血管性状与疾病的单核苷酸多态性（single nucleotide polymorphism, SNP）遗传力存在显著富集。尤为关键的是，我们可为多种代谢性状优先筛选出胃部特异性候选基因：例如参与葡萄糖代谢的NQO1、参与嘌呤与蛋白质代谢的MUC1，以及作为体重与体组成调控因子的RAB27B。本研究的胃体与胃窦黏膜活检样本，均采集自多达431名健康个体的常规胃镜检查；我们利用RNA测序（RNA-seq）获得的数据，完成了这两个主要胃部区域的基因表达谱分析。