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使用 UAE 患者的转录组谱鉴定 1 型糖尿病并发症中的新型差异表达基因:一项多中心研究。

Identification of novel differentially expressed genes in type 1 diabetes mellitus complications using transcriptomic profiling of UAE patients: a multicenter study.

机构信息

Basic Medical Science Department, College of Medicine, University of Sharjah, P.O. Box: 27272, Sharjah, United Arab Emirates.

Department of Physiology and Immunology, College of Medicine, Khalifa University, Abu Dhabi, United Arab Emirates.

出版信息

Sci Rep. 2022 Sep 29;12(1):16316. doi: 10.1038/s41598-022-18997-w.

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disorder that mainly affects children and young adults. It is associated with debilitating and long-life complications. Therefore, understanding the factors that lead to the onset and development of these complications is crucial. To our knowledge this is the first study that attempts to identify the common differentially expressed genes (DEGs) in T1DM complications using whole transcriptomic profiling in United Arab Emirates (UAE) patients. The present multicenter study was conducted in different hospitals in UAE including University Hospital Sharjah, Dubai Hospital and Rashid Hospital. A total of fifty-eight Emirati participants aged above 18 years and with a BMI < 25 kg/m were recruited and forty-five of these participants had a confirmed diagnosis of T1DM. Five groups of complications associated with the latter were identified including hyperlipidemia, neuropathy, ketoacidosis, hypothyroidism and polycystic ovary syndrome (PCOS). A comprehensive whole transcriptomic analysis using NGS was conducted. The outcomes of the study revealed the common DEGs between T1DM without complications and T1DM with different complications. The results revealed seven common candidate DEGs, SPINK9, TRDN, PVRL4, MYO3A, PDLIM1, KIAA1614 and GRP were upregulated in T1DM complications with significant increase in expression of SPINK9 (Fold change: 5.28, 3.79, 5.20, 3.79, 5.20) and MYO3A (Fold change: 4.14, 6.11, 2.60, 4.33, 4.49) in hyperlipidemia, neuropathy, ketoacidosis, hypothyroidism and PCOS, respectively. In addition, functional pathways of ion transport, mineral absorption and cytosolic calcium concentration were involved in regulation of candidate upregulated genes related to neuropathy, ketoacidosis and PCOS, respectively. The findings of this study represent a novel reference warranting further studies to shed light on the causative genetic factors that are involved in the onset and development of T1DM complications.

摘要

1 型糖尿病(T1DM)是一种主要影响儿童和年轻人的慢性代谢紊乱。它与使人衰弱和终身的并发症有关。因此,了解导致这些并发症发生和发展的因素至关重要。据我们所知,这是第一项尝试使用阿联酋(UAE)患者的全转录组谱分析来识别 T1DM 并发症中常见差异表达基因(DEG)的研究。本多中心研究在阿联酋的不同医院进行,包括沙迦大学医院、迪拜医院和拉希德医院。共招募了 58 名年龄在 18 岁以上且 BMI<25kg/m 的阿联酋参与者,其中 45 名参与者被确诊为 T1DM。确定了与后者相关的 5 组并发症,包括高血脂、神经病、酮症酸中毒、甲状腺功能减退症和多囊卵巢综合征(PCOS)。使用 NGS 进行了全面的全转录组分析。研究结果揭示了 T1DM 无并发症与 T1DM 不同并发症之间的常见 DEG。结果显示,在 T1DM 并发症中,有 7 个共同的候选 DEG,SPINK9、TRDN、PVRL4、MYO3A、PDLIM1、KIAA1614 和 GRP 上调,SPINK9 的表达显著增加(倍数变化:5.28、3.79、5.20、3.79、5.20)和 MYO3A(倍数变化:4.14、6.11、2.60、4.33、4.49)在高血脂、神经病、酮症酸中毒、甲状腺功能减退症和 PCOS 中分别上调。此外,离子转运、矿物质吸收和细胞质钙浓度的功能途径参与了与神经病、酮症酸中毒和 PCOS 相关的候选上调基因的调节。这项研究的结果代表了一个新的参考,需要进一步的研究来阐明参与 T1DM 并发症发生和发展的致病遗传因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c25/9523055/075da108254e/41598_2022_18997_Fig1_HTML.jpg

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