Discovering Genetic Risk Factors for COVID-19 Infection: A Breakthrough by the COVID-19 Genetics Project

2023-09-15 03:20:45

Date: 15 September 2023, Medical Genome Center Faculty of Medicine Ramathibodi Hospital Mahidol University Posted a message on the Facebook page “Center for Medical Genomics” stating…

International research team of “The COVID-19 Genetics Project (COVID-19 HGI)” announced the discovery of 28 new genes that increase the risk of COVID-19 infection. who may be critically ill and 1 gene that has the opposite effect, which increases the risk of COVID-19 infection but showing no symptoms

The COVID-19 Host Genetics Initiative (COVID-19 HGI) is a large international project analyzing data from 82 studies in 35 countries, with collaborators around the world. Up to 3,669 people and more than 219,692 volunteers who were severely infected with COVID-19 were hospitalized and more than 3 million people who were infected but had mild symptoms participated in the project. It has been operated continuously for 4 years. Year since the start of the COVID-19 outbreak Research results have been published periodically. Most recently published in the medical academic journal “Nature” on September 6, 2023.

COVID-19 Genetics Project It clearly shows that in addition to the important risk factors being the elderly group. People with chronic illnesses and pregnant women Also known as “Vulnerable Population 608” In addition to genetic factors, they also play an important role in identifying people at high risk of contracting COVID-19. at a critical level

note

Vulnerable group 608

Group 1: Elderly people aged 60 years and over.

Group 2: People with 7 diseases including:

1. Chronic respiratory disease

2. Cardiovascular disease

3. Chronic kidney disease

4. Stroke

5. Obesity

6. Cancer

7. Diabetes

Group 3: Pregnant women

Discovering genetic risk factors is critical to helping scientists develop precision medicine to prevent and treat COVID-19 in the future.

These genetic factors are linked to critical illness. Hospital admission and the rate of difficulty of infection COVID-19 Genetics Project Able to identify gene groups related to The process by which viruses enter cells The process of preventing viruses from being transmitted to the respiratory tract through mucus. and the type 1 interferon response in combating COVID-19.

A clear example is those who have the gene “HLA-B*15:01” inherited from both parents is more likely to result in COVID-19 infection. who are asymptomatic than people with HLA-B*other genotypes up to 8 times

The COVID-19 Genetics Project (COVID-19 HGI) is a large-scale international project led by the “Broad Institute” in the United States and the “Institute for Molecular Medicine Finland (FIMM)” in Finland. The results of the analysis are analyzed. (meta-analysis) of 82 sub-projects in 35 countries, involving 3,669 participants, with subjects with severe infections. More than 219,692 people were hospitalized (case study) and more than 3 million people were infected but had mild symptoms as a control group (control study) participating in the project. It has been operated continuously throughout the 4 years of the COVID-19 outbreak. There are research results published periodically. Most recently published in the medical academic journal “Nature” on September 6, 2023.

Research published recently in the journal Nature identified 51 locations on the human genome that are associated with susceptibility to infection. (susceptibility) critical severe infection (severity) virus entry into cells (viral entry) prevention of COVID-19 infection in the respiratory system through the mucous membrane (airway defense in mucus) and the type I interferon response (type I interferon response)

Of the 51 locations on the human genome found

36 positions tend to result in greater disease severity. (hospital treatment)

9 loci likely to influence greater susceptibility to SARS-CoV-2 infection, and

6 positions cannot yet classify related duties.

1. Important gene groups involved in the path of viruses into cells:

– SLC6A20: is a gene that creates a protein that interacts with the spikes of the SARS-CoV-2 virus, which is used for attaching and inserting itself into the cells of an infected person.

– ABO: Relationship between the ABO blood group gene. Antibodies produced by the body against blood group A and against blood group B may interfere with the virus’ entry into cells.

– SFTPD: Gene involved in the production of lung cell surface protein “D (SP-D),” which helps create lung innate immune molecules and a protective response against viral infections in the lung lining.

– ACE2: is a gene that creates a protein on the cell surface for SARS-CoV-2 to attach to before inserting itself into cells.

– TMPRSS2: is a gene that creates a protein that changes the spikes of the virus to attach to the cell surface and insert into the cell.

2. Important gene groups involved in protection against viral infection through the mucous membrane of the respiratory tract:

– MUC1/THBS3: MUC1 is an important mucus-producing gene of the respiratory system that protects against microbial and viral invasion.

– MUC5B: Gene that creates the main component of mucus in the respiratory tract that helps eliminate germs that attach to the mucous membrane.

– MUC4: An important respiratory mucus-producing gene that protects against microbial and viral invasion.

– MUC16: An important respiratory mucus-producing gene that protects against microbial and viral invasion.

3. Important genes involved in type I interferon response: These are genes that produce cytokines (cytokines) produced by T-cell lymphocytes that play an important role in destroying viruses and invading microorganisms.

– IFNAR2: Mutations in the IFNAR2 gene, which is part of the type 1 interferon system, increase the risk of COVID-19 infection. who must be hospitalized and have a serious illness

– OAS1: is a gene that produces an important cytokine in the type 1 interferon system.

– TYK2: The tyrosine kinase 2 (TYK2) gene is a gene that produces cytokines in the type 1 interferon system.

– JAK1: Janus kinase (JAK) is a gene that produces cytokines in the type 1 interferon system.

– IRF1: is a gene that produces cytokines in the interferon system type 1.

– IFNα10: is a gene that creates a protein that specifically binds to IFNα.

These genes are involved in immune system mechanisms. Mutations in these genes are responsible for sensitivity. (susceptibility) to infection and severity of COVID-19 infection (severity), which is extremely important knowledge in the development of antiviral drugs-19 in the future.

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