COVID-19における重症疾患の遺伝的メカニズム
Erola Pairo-Castineira1,2, Sara Clohisey1, Lucija Klaric2
1Roslin Institute, University of Edinburgh, Edinburgh, UK.
Nature
|December 11, 2020
まとめ
深刻なCOVID-19患者の遺伝子変異は,新たな治療目標を示しています. 抗ウイルス防御と炎症に関与する重要な遺伝子は,2019年の重症コロナウイルス病に対する薬剤の再利用の可能性を示唆する.
科学分野:
- 遺伝学
- 免疫学
- クリティカル ケア 医療
背景:
- ホストによる肺炎は,重篤なCOVID-19患者の死亡率に大きく寄与する.
- 宿主の遺伝的要因を特定することは,病気のメカニズムを理解し,新しい治療法を開発するために不可欠です.
研究 の 目的:
- 重症なCOVID-19患者の全ゲノム関連研究 (GWAS) を実施し,重症疾患に関連する遺伝的変異を特定する.
- 特定された遺伝的関連の機能的影響を分析することによって,潜在的な治療目標を探求する.
主な方法:
- クリティカルケアにおける死亡率の遺伝学 (GenOMICC) 研究は,英国の集中治療室から2,244人の重症のCOVID-19患者を分析した.
- ゲノム全体の有意な関連が特定され,複製されました.
- メンデルのランダム化とトランスクリプトーム全体の関連研究は,遺伝子発現と疾患関連を調査するために使用されました.
主要な成果:
- 4つの新しい全ゲノム有意な関連が特定されました: rs10735079 (OAS1/2/3クラスター),rs74956615 (TYK2に近い),rs2109069 (DPP9),およびrs2236757 (IFNAR2).
- IFNAR2の低発現とTYK2の高発現は,生命を脅かすCOVID-19と関連していました.
- 肺組織におけるCCR2の高い発現は,重度のCOVID-19と相関する.
結論:
- 遺伝的発見は,宿主の抗ウイルス反応と重度のCOVID-19における炎症経路の役割を強調しています.
- 特定された遺伝子や経路は 既存の薬物の再利用の ターゲットとなる可能性があります
- これらの発見を検証し,臨床実践の変更を導くために,さらなる大規模なランダム化臨床試験が必要である.
関連する概念動画
Pneumonia II: Pathophysiology
2.0K
The pathophysiology of pneumonia involves the following steps:
2.0K
COPD: Pathogenesis and Clinical Features
1.6K
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...
1.6K
Single Nucleotide Polymorphisms-SNPs
17.4K
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,...
17.4K
Factors Affecting the Risk of Infection
13.1K
The hosts' susceptibility to infection depends on several factors. The integrity of the skin and mucous membranes helps protect the body against microbial attacks. When the skin is altered, the chance of infection, limb loss, and even death increases.
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...
13.1K
Cystic Fibrosis: Pathogenesis
570
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,...
570
Cancer-Critical Genes I: Proto-oncogenes
10.0K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.0K


