Hu Qian, Luo Yunfang, He Hao, Chen Hua, Liao Di
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Key Laboratory of Medical Genetics of Hunan Province, Central South University, Changsha, Hunan, China.
Heliyon. 2024 Jul 30;10(15):e35453. doi: 10.1016/j.heliyon.2024.e35453. eCollection 2024 Aug 15.
and design: Considering the clinical link between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS), we performed bioinformatics analysis to uncover their pathogenic interrelationship.
Data from the U.S. National Health and Nutritional Examination Survey (NHANES) 1999-2018 were included. Among 4851 participants in NHANES, NAFLD was significantly associated with atherosclerotic cardiovascular disease risk (ASCVD risk) (OR = 2.32, 95%CI: 2.04-2.65, P < 0.0001). We conducted WGCNA analysis for NAFLD (GSE130970) and AS (GSE28829) and identified three modules positively related to NAFLD severity and two modules accelerating atherosclerosis plaque progression. 198 key-modules genes were obtained via overlapping these modules. Next, we mined the disease-controlled differentially expressed genes (DEGs) from NAFLD (GSE89632) and AS (GSE100927), respectively. The final common risk genes (, , , , , , and ) were defined by intersecting the upregulated DEGs with 198 genes and validated in new datasets (GSE48452 and GSE43292). Importantly, they showed good diagnostic ability for NAFLD and AS. Immune infiltration analysis showed both illnesses have dysregulated immunity. Analysis of single-cell sequencing datasets NAFLD (GSE179886) and AS (GSE159677) uncovered different abnormal expressions of seven common genes in different immune cells while highlighting metabolic disturbances including upregulation of fatty acid biosynthesis, downregulation of fatty acid degradation and elongation.
We found 7 shared hub genes with good diagnostic ability and depicted the landscapes of immune and metabolism involved in NAFLD and AS. Our results provided a comprehensive association between them and may contribute to developing potential intervention strategies for targeting both disorders based on these risk factors.
考虑到非酒精性脂肪性肝病（NAFLD）与动脉粥样硬化（AS）之间的临床联系，我们进行了生物信息学分析以揭示它们的致病相互关系。
纳入了1999 - 2018年美国国家健康与营养检查调查（NHANES）的数据。在NHANES的4851名参与者中，NAFLD与动脉粥样硬化性心血管疾病风险（ASCVD风险）显著相关（OR = 2.32，95%CI：2.04 - 2.65，P < 0.0001）。我们对NAFLD（GSE130970）和AS（GSE28829）进行了加权基因共表达网络分析（WGCNA），并确定了与NAFLD严重程度呈正相关的三个模块以及加速动脉粥样硬化斑块进展的两个模块。通过重叠这些模块获得了198个关键模块基因。接下来，我们分别从NAFLD（GSE89632）和AS（GSE100927）中挖掘疾病对照差异表达基因（DEGs）。最终的共同风险基因（、、、、、和）通过将上调的DEGs与198个基因相交来定义，并在新数据集（GSE48452和GSE43292）中进行了验证。重要的是，它们对NAFLD和AS显示出良好的诊断能力。免疫浸润分析表明两种疾病都存在免疫失调。对单细胞测序数据集NAFLD（GSE179886）和AS（GSE159677）的分析揭示了七个共同基因在不同免疫细胞中的不同异常表达，同时突出了代谢紊乱，包括脂肪酸生物合成上调、脂肪酸降解和延长下调。
我们发现了7个具有良好诊断能力的共享枢纽基因，并描绘了NAFLD和AS中免疫和代谢的图景。我们的结果提供了它们之间的全面关联，并可能有助于基于这些风险因素制定针对这两种疾病的潜在干预策略。
