在男性中,CYP19A1调解了严重的SARS-CoV-2疾病结果
Stephanie Stanelle-Bertram1, Sebastian Beck1, Nancy Kouassi Mounogou1
1Department for Viral Zoonoses - One Health, Leibniz Institute of Virology, Hamburg, Germany.
Cell reports. Medicine
|August 12, 2023
概括
编码芳酶的CYP19A1基因在男性中恶化了严重的COVID-19. 用莱特醇抑制这种酶可能为男性患者提供一种新的治疗策略.
科学领域:
- 遗传学和分子生物学
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 男性性别是严重的COVID-19的重要危险因素.
- 性别特定的COVID-19严重程度背后的机制尚不清楚.
研究的目的:
- 为了识别导致性取决于COVID-19结果的宿主因素.
- 调查CYP19A1 (芳酶) 在男性SARS-CoV-2感染严重性中的作用.
主要方法:
- 使用机器学习分析来自COVID-19队列 (n=2,866) 的外基因组测序数据.
- 检查人类尸检衍生的肺组织 (n=86).
- 在体内研究使用黄金仓鼠模型的SARS-CoV-2感染,包括用CYP19A1抑制剂 (莱特) 治疗.
主要成果:
- 增加CYP19A1活性的突变与男性的严重COVID-19相关,但与女性无关.
- 与女性相比,已故男性观察到肺部CYP19A1表达的增加.
- SARS-CoV-2 感染在雄性仓鼠中增加了肺部 CYP19A1 表达,导致荷尔蒙失衡和肺功能减弱.
- 莱特醇治疗改善了肺功能,并恢复了受感染雄性仓鼠的性激素平衡.
结论:
- CYP19A1被确定为一个关键的宿主因素,有助于男性的SARS-CoV-2感染的性别特异性严重程度.
- 用莱特醇抑制CYP19A1为治疗受影响男性的严重COVID-19提供了潜在的治疗途径.
相关概念视频
Cystic Fibrosis: Pathogenesis
281
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
281
Single Nucleotide Polymorphisms-SNPs
15.3K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.3K
The Y Chromosome Determines Maleness
6.7K
The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
6.7K
COPD: Pathogenesis and Clinical Features
344
Chronic obstructive pulmonary disease (COPD) is a group of lung conditions that progressively worsen over time, including chronic bronchitis and emphysema. This cluster of diseases collectively leads to a gradual and irreversible decline in lung function over time.
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
344
Chronic Obstructive Pulmonary Disease-II: Pathophysiology
2.8K
Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Inflammation
2.8K
Infertility in Males
295
Male infertility affects millions of couples worldwide, arising from various factors that impact different stages of the reproductive process. An endocrine imbalance resulting from conditions like hypogonadism, Klinefelter syndrome, or pituitary disorders can disrupt hormone levels and reduce sperm production. Testicular defects, such as tumors, cryptorchidism, atrophic testes, abnormal sperm morphology, and low sperm count or motility, may arise due to genetic factors, structural...
295


