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Hepatic steatosis and steatohepatitis: a functional meta-analysis of sex-based differences in transcriptomic studies
Biology of Sex Differences ( IF 7.9 ) Pub Date : 2021-03-25 , DOI: 10.1186/s13293-021-00368-1
José F Català-Senent 1, 2 , Marta R Hidalgo 1 , Marina Berenguer 3, 4, 5, 6 , Gopanandan Parthasarathy 7 , Harmeet Malhi 7 , Pablo Malmierca-Merlo 1, 8 , María de la Iglesia-Vayá 9 , Francisco García-García 1, 2
Affiliation  

Previous studies have described sex-based differences in the epidemiological and clinical patterns of non-alcoholic fatty liver disease (NAFLD); however, we understand relatively little regarding the underlying molecular mechanisms. Herein, we present the first systematic review and meta-analysis of NAFLD transcriptomic studies to identify sex-based differences in the molecular mechanisms involved during the steatosis (NAFL) and steatohepatitis (NASH) stages of the disease. Transcriptomic studies in the Gene Expression Omnibus database were systematically reviewed following the PRISMA statement guidelines. For each study, NAFL and NASH in premenopausal women and men were compared using a dual strategy: gene-set analysis and pathway activity analysis. Finally, the functional results of all studies were integrated into a meta-analysis. We reviewed a total of 114 abstracts and analyzed seven studies that included 323 eligible patients. The meta-analyses identified significantly altered molecular mechanisms between premenopausal women and men, including the overrepresentation of genes associated with DNA regulation, vinculin binding, interleukin-2 responses, negative regulation of neuronal death, and the transport of ions and cations in premenopausal women. In men, we discovered the overrepresentation of genes associated with the negative regulation of interleukin-6 and the establishment of planar polarity involved in neural tube closure. Our meta-analysis of transcriptomic data provides a powerful approach to identify sex-based differences in NAFLD. We detected differences in relevant biological functions and molecular terms between premenopausal women and men. Differences in immune responsiveness between men and premenopausal women with NAFLD suggest that women possess a more immune tolerant milieu, while men display an impaired liver regenerative response.

中文翻译:

肝脂肪变性和脂肪性肝炎:转录组学研究中性别差异的功能性荟萃分析

以前的研究描述了非酒精性脂肪肝 (NAFLD) 的流行病学和临床模式的性别差异;然而,我们对潜在的分子机制了解相对较少。在此,我们首次对 NAFLD 转录组学研究进行系统评价和荟萃分析,以确定该疾病脂肪变性 (NAFL) 和脂肪性肝炎 (NASH) 阶段所涉及的分子机制的性别差异。基因表达综合数据库中的转录组学研究按照 PRISMA 声明指南进行了系统审查。对于每项研究,使用双重策略比较绝经前女性和男性的 NAFL 和 NASH:基因集分析和通路活性分析。最后,将所有研究的功能结果整合到荟萃分析中。我们共审查了 114 篇摘要并分析了 7 项研究,其中包括 323 名符合条件的患者。荟萃分析确定了绝经前女性和男性之间显着改变的分子机制,包括与 DNA 调节、纽蛋白结合、白细胞介素 2 反应、神经元死亡的负调节以及离子和阳离子转运相关的基因的过度表达。在男性中,我们发现与白细胞介素 6 的负调节和神经管闭合所涉及的平面极性的建立相关的基因表达过多。我们对转录组数据的荟萃分析提供了一种强大的方法来识别 NAFLD 中基于性别的差异。我们检测到绝经前女性和男性在相关生物学功能和分子术语方面的差异。
更新日期:2021-03-26
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