肝脏和脂肪组织中的血皮质醇相关基因网络涉及皮质类固醇结合型球蛋白在调节组织葡萄皮质类固醇作用和心血管风险方面
Sean Bankier1,2,3, Lingfei Wang3, Andrew Crawford1,4
1University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Frontiers in endocrinology
|September 25, 2023
概括
他们发现皮质醇,皮质类固醇结合型全球蛋白 (CBG) 和心血管疾病 (CVD) 之间的遗传联系. 这项研究揭示了CBG变异如何影响基因网络,可能导致心血管疾病.
科学领域:
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
- 心血管科学 心血管科学
背景情况:
- 全基因组关联元分析确定了与血皮质醇,心血管疾病 (CVD) 和皮质类固醇结合型球蛋白 (CBG) 生产相关的遗传变异.
- 较高的血皮质醇水平与心血管疾病有因果关系,但涉及CBG变异的机制尚不清楚.
研究的目的:
- 研究CBG变异影响心血管疾病风险的机制.
- 在各种组织中识别由皮质醇及其受体 (GR) 调节的基因网络.
主要方法:
- 利用来自STARNET研究的基因组和转录组数据.
- 采用单核酸多态 (SNPs) 和跨关联来连接七种组织类型的皮质醇相关基因.
- 应用因果推断和 cis 表达量特征定位 (eQTL) 来重建基因网络.
主要成果:
- 与皮质醇相关的SNP显示出与肝脏,皮下脂肪和内脏腹部脂肪中的基因的跨关联.
- 鉴定了皮质醇调节基因,包括那些受葡萄糖皮质体受体 (GR) 影响的基因.
- 重建的组织特异性基因网络,特别是由IRF2.2调节的皮下脂肪网络.
结论:
- 肝脏CBG产生的变化会扰乱外围组织中皮质醇调节的基因网络.
- 这些干扰提供了一个合理的途径,将CBG变异与心血管疾病发展联系起来.
相关概念视频
Hormones of the Adrenal Glands
2.5K
Adrenal hormones play a pivotal role in maintaining the body's electrolyte balance and orchestrating responses to stress, showcasing the intricate functions of the adrenal cortex and medulla.
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
2.5K
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
Hypothalamic-Pituitary Axis
60.4K
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
60.4K
Global Regulatory Systems
41
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
41
GPCRs Regulate Adenylyl Cylase Activity
5.7K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
Target Cell Response to Hormones
3.1K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
3.1K


