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Variability in genes related to SARS-CoV-2 entry into host cells (ACE2, TMPRSS2, TMPRSS11A, ELANE, and CTSL) and its potential use in association studies.
Vargas-Alarcón, Gilberto; Posadas-Sánchez, Rosalinda; Ramírez-Bello, Julian.
  • Vargas-Alarcón G; Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: gvargas63@yahoo.com.
  • Posadas-Sánchez R; Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
  • Ramírez-Bello J; Research Unit, Hospital Juárez de México, Mexico City, Mexico.
Life Sci ; 260: 118313, 2020 Nov 01.
Article in English | MEDLINE | ID: covidwho-725734
ABSTRACT

BACKGROUND:

The prevalence and mortality of the outbreak of the COVID-19 pandemic show marked geographic variation. The presence of several subtypes of the coronavirus and the genetic differences in the populations could condition that variation. Thus, the objective of this study was to propose variants in genes that encode proteins related to the SARS-CoV-2 entry into the host cells as possible targets for genetic associations studies.

METHODS:

The allelic frequencies of the polymorphisms in the ACE2, TMPRSS2, TMPRSS11A, cathepsin L (CTSL), and elastase (ELANE) genes were obtained in four populations from the American, African, European, and Asian continents reported in the 1000 Genome Project. Moreover, we evaluated the potential biological effect of these variants using different web-based tools.

RESULTS:

In the coding sequences of these genes, we detected one probably-damaging polymorphism located in the TMPRSS2 gene (rs12329760) that produces a change of amino acid. Furthermore, forty-eight polymorphisms with possible functional consequences were detected in the non-coding sequences of the following genes three in ACE2, seventeen in TMPRSS2, ten in TMPRSS11A, twelve in ELANE, and six in CTSL. These polymorphisms produce binding sites for transcription factors and microRNAs. The minor allele frequencies of these polymorphisms vary in each community; indeed, some of them are high in specific populations.

CONCLUSION:

In summary, using data of the 1000 Genome Project and web-based tools, we propose some polymorphisms, which, depending on the population, could be used for genetic association studies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Polymorphism, Genetic / Serine Endopeptidases / Coronavirus Infections / Peptidyl-Dipeptidase A / Leukocyte Elastase / Cathepsin L / Serine Proteases / Betacoronavirus / Membrane Proteins Type of study: Experimental Studies / Observational study Topics: Variants Limits: Humans Language: English Journal: Life Sci Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Polymorphism, Genetic / Serine Endopeptidases / Coronavirus Infections / Peptidyl-Dipeptidase A / Leukocyte Elastase / Cathepsin L / Serine Proteases / Betacoronavirus / Membrane Proteins Type of study: Experimental Studies / Observational study Topics: Variants Limits: Humans Language: English Journal: Life Sci Year: 2020 Document Type: Article