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脂代谢和神经肌肉接头作为勃起功能障碍和阻塞性睡眠呼吸暂停遗传基础的共同途径。

Lipid metabolism and neuromuscular junction as common pathways underlying the genetic basis of erectile dysfunction and obstructive sleep apnea.

机构信息

Sleep Institute, São Paulo, Brazil.

Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.

出版信息

Int J Impot Res. 2024 Sep;36(6):614-620. doi: 10.1038/s41443-023-00795-1. Epub 2023 Nov 21.

Abstract

Erectile dysfunction (ED) incidence is higher in patients with obstructive sleep apnea (OSA). Studies have suggested that ED and OSA may activate similar pathways; however, few have investigated the links between their underlying genotypic profiles. Therefore, we conducted an in-silico analysis to test whether ED and OSA share genetic variants of risk and to identify any molecular, cellular and biological interactions between them. Two gene lists were manually curated through a literature review based on a PUBMED search, which resulted in one gene list associated with ED (total of 205 genes) and the other with OSA (total of 2622 genes). Between those gene sets, 35 were common for both lists (Fisher exact test, p-value = 0.027). The Protein-protein interaction (PPI) analysis using the intersect list as input showed that 3 of them had direct interactions (LPL, DGKB and PLCB1). In addition, the biological function of the genes contained in the intersect list suggested that pathways related to lipid metabolism and the neuromuscular junction were commonly found in the genetic basis of ED and OSA. From the shared genes between both conditions, the biological pathways highlighted in this study may serve as preliminary findings for future functional investigations on OSA and ED association.

摘要

勃起功能障碍 (ED) 在阻塞性睡眠呼吸暂停 (OSA) 患者中的发病率更高。研究表明,ED 和 OSA 可能激活相似的途径;然而,很少有研究调查它们潜在的基因型谱之间的联系。因此,我们进行了一项计算机分析,以测试 ED 和 OSA 是否具有共同的风险遗传变异,并确定它们之间的任何分子、细胞和生物学相互作用。通过基于 PUBMED 搜索的文献回顾,手动整理了两份基因列表,其中一份与 ED 相关(共 205 个基因),另一份与 OSA 相关(共 2622 个基因)。在这些基因集中,有 35 个基因在两个列表中是共同的(Fisher 精确检验,p 值=0.027)。使用交集列表作为输入的蛋白质-蛋白质相互作用 (PPI) 分析表明,其中 3 个具有直接相互作用(LPL、DGKB 和 PLCB1)。此外,交集列表中包含的基因的生物学功能表明,与脂质代谢和神经肌肉接头相关的途径在 ED 和 OSA 的遗传基础中普遍存在。从两种情况下共同的基因来看,本研究中突出的生物学途径可能为未来关于 OSA 和 ED 关联的功能研究提供初步发现。

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