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Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans

Zewen Sun1, Lin Pan2, Aowen Tian3

  • 1Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|April 18, 2024
PubMed

Insights

Natural selection has led to increased CCR3 expression in Sub-Saharan Africans, offering resistance to critical COVID-19. This suggests CCR3 as a potential therapeutic target for severe COVID-19.

Area of Science:

  • Genetics
  • Evolutionary Biology
  • Immunology

Background:

  • COVID-19 critical illness prevalence varies among ethnicities.
  • Genetic factors are suspected to influence this variation.
  • Sub-Saharan Africans exhibit differential susceptibility to severe COVID-19.

Purpose of the Study:

  • Investigate natural selection signals in genes linked to critical COVID-19 in Sub-Saharan Africans.
  • Identify genetic mechanisms underlying COVID-19 severity variation.
  • Explore CCR3 as a potential therapeutic target.

Main Methods:

  • Analysis of severe COVID-19 Single Nucleotide Polymorphisms (SNPs) from HGI.
  • Assessment of selection signals using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (XP-EHH), and fixation index (Fst) in 661 Sub-Saharan Africans.
  • Allele frequency trajectory analysis of ancient DNA and Mendelian randomization.

Main Results:

  • Significant natural selection signals were identified for the CCR3 gene in Sub-Saharan Africans.
  • The CCR3 variant rs17217831-A showed strong selection signals (high iHS and XP-EHH).
  • Natural selection increased CCR3 expression, which, along with eosinophil counts, was associated with reduced risk of critical COVID-19.

Conclusions:

  • Sub-Saharan Africans exhibit natural resistance to critical COVID-19 due to evolutionary selection.
  • CCR3 is identified as a key gene under selection, influencing COVID-19 severity.
  • CCR3 presents a potential novel therapeutic target for mitigating severe COVID-19 outcomes.

Keywords:
CCR3COVID-19Mendelian RandomizationNatural selection

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