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Pharmacogenomics of genetic polymorphism within the genes responsible for SARS-CoV-2 susceptibility and the drug-metabolising genes used in treatment.

ABSTRACT: The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a significant challenge to international health. Pharmacogenomics aims to identify the different genetic variations that exist between individuals and populations in order to determine appropriate treatment protocols to enhance the efficacy of drugs and reduce their side-effects. This literature review provides an overview of recent studies of genetic polymorphisms in genes that mediate the SARS-CoV-2 infection mechanism (ACE1, ACE2, TMPRSS2 and CD26). In addition, genetic variations in the drug-metabolising enzyme genes of several selected drugs used in the treatment of COVID-19 are summarised. This may help construct an effective health protocol based on genetic biomarkers to optimise response to treatment. Potentially, pharmacogenomics could contribute to the development of effective high-throughput assays to improve patient evaluation, but their use will also create ethical, medical, regulatory, and legal issues, which should now be considered in the era of personalised medicine.

SUBMITTER: Al-Eitan LN

PROVIDER: S-EPMC7744885 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Pharmacogenomics of genetic polymorphism within the genes responsible for SARS-CoV-2 susceptibility and the drug-metabolising genes used in treatment.

Al-Eitan Laith N LN Alahmad Saif Z SZ

Reviews in medical virology 20201117 4

The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a significant challenge to international health. Pharmacogenomics aims to identify the different genetic variations that exist between individuals and populations in order to determine appropriate treatment protocols to enhance the efficacy of drugs and reduce their side-effects. This literature review provides an overview of recent studies of genetic polymorphisms in genes that mediate the SARS-CoV-2 ...[more]

PMID: 33205496

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Project description:There is considerable variability in the susceptibility and progression for COVID-19 and it appears to be strongly correlated with age, gender, ethnicity and pre-existing health conditions. However, to our knowledge, cohort studies of COVID-19 in clinically vulnerable groups are lacking. Host genetics has also emerged as a major risk factor for COVID-19, and variation in the ACE2 receptor, which facilitates entry of the SARS-CoV-2 virus into the cell, has become a major focus of attention. Thus, we interrogated an ethnically diverse cohort of National Health Service (NHS) patients in the United Kingdom (United Kingdom) to assess the association between variants in the ACE2 locus and COVID-19 risk. We analysed whole-genome sequencing (WGS) data of 1,837 cases who were tested positive for SARS-CoV-2, and 37,207 controls who were not tested, from the UK's 100,000 Genomes Project (100KGP) for the presence of ACE2 coding variants and extract expression quantitative trait loci (eQTLs). We identified a splice site variant (rs2285666) associated with increased ACE2 expression with an overrepresentation in SARS-CoV-2 positive patients relative to 100KGP controls (p = 0.015), and in hospitalised European patients relative to outpatients in intra-ethnic comparisons (p = 0.029). We also compared the prevalence of 288 eQTLs, of which 23 were enriched in SARS-CoV-2 positive patients. The eQTL rs12006793 had the largest effect size (d = 0.91), which decreases ACE2 expression and is more prevalent in controls, thus potentially reducing the risk of COVID-19. We identified three novel nonsynonymous variants predicted to alter ACE2 function, and showed that three variants (p.K26R, p. H378R, p. Y515N) alter receptor affinity for the viral Spike (S) protein. Variant p. N720D, more prevalent in the European population (p < 0.001), potentially increases viral entry by affecting the ACE2-TMPRSS2 complex. The spectrum of genetic variants in ACE2 may inform risk stratification of COVID-19 patients and could partially explain the differences in disease susceptibility and severity among different ethnic groups.

Dataset Information

Pharmacogenomics of genetic polymorphism within the genes responsible for SARS-CoV-2 susceptibility and the drug-metabolising genes used in treatment.

Publications

Pharmacogenomics of genetic polymorphism within the genes responsible for SARS-CoV-2 susceptibility and the drug-metabolising genes used in treatment.

Similar Datasets

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