Fadaie Mahmood, Khalafiyan Anis, Ghafouri Elham, Ranjbarnejad Tayebeh, Moein Shiva
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Adv Biomed Res. 2024 Jul 29;13:42. doi: 10.4103/abr.abr_229_23. eCollection 2024.
Celiac disease (CeD) is an autoimmune enteropathy triggered by dietary gluten. Almost 90% of CeD patients have HLA-DQ2 or -DQ8 haplotypes. As a high proportion of first-degree relatives (FDRs) of CeD patients have the same haplotype, it is assumed that they are at a higher risk of disease development than the general population. Nevertheless, the prevalence of CeD among FDRs is considerably low (7.5%).
In order to figure out this discrepancy, a microarray dataset of intestinal mucosal biopsies of CeD patients, FDRs, and control groups was reanalyzed, and a protein-protein interaction network was constructed.
Principal component analysis showed that CeD and FDR groups are far away in terms of gene expression. Comparing differentially expressed genes of both networks demonstrated inverse expression of some genes mainly related to cell cycle mechanisms. Moreover, analysis of the modular structures of up- and downregulated gene networks determined activation of protein degradation mechanisms and inhibition of ribosome-related protein synthesis in celiac patients with an upside-down pattern in FDRs.
The top-down systems biology approach determined some regulatory pathways with inverse function in CeD and FDR groups. These genes and molecular mechanisms could be a matter of investigation as potential druggable targets or prognostic markers in CeD.
乳糜泻（CeD）是一种由膳食麸质引发的自身免疫性肠病。近90%的CeD患者具有HLA - DQ2或 - DQ8单倍型。由于CeD患者的一级亲属（FDRs）中有很大比例具有相同的单倍型，因此推测他们比普通人群患该病的风险更高。然而，FDRs中CeD的患病率相当低（7.5%）。
为了弄清楚这种差异，重新分析了CeD患者、FDRs和对照组的肠道黏膜活检芯片数据集，并构建了蛋白质 - 蛋白质相互作用网络。
主成分分析表明，CeD组和FDR组在基因表达方面差异很大。比较两个网络的差异表达基因发现，一些主要与细胞周期机制相关的基因呈反向表达。此外，对上调和下调基因网络的模块结构分析确定，乳糜泻患者中蛋白质降解机制被激活，核糖体相关蛋白质合成受到抑制，而FDRs中则呈现相反模式。
自上而下的系统生物学方法确定了CeD组和FDR组中一些具有相反功能的调控途径。这些基因和分子机制可能作为CeD潜在的可药物作用靶点或预后标志物进行研究。
