Genetic landscape of the ACE2 coronavirus receptor

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SARS-CoV-2 enters human cells via ACE2 (angiotensin converting enzyme protein as a receptor. Thus, ACE2 is essential for coronavirus infection and treatment. ACE2 is abundantly expressed in the cardiac, pulmonary, and gastrointestinal tracts, where it plays critical regulatory roles in cardiovascular and other biological systems. The genetic origin of ACE2 protein levels, on the other hand, is poorly understood. .

For one study, researchers performed the largest genome-wide association meta-analysis of plasma ACE2 levels in the SCALLOP consortium, involving more than 28,000 people (systematic and combined Olink protein analysis). Cross-sectional epidemiological correlations of circulating ACE2 were discussed. They assessed important genetic associations with cardiometabolic phenotypes, COVID-19, and other complex human characteristics and disorders using the high-definition likelihood technique based on summary statistics. They use Mendelian randomization to predict the effect of soluble ACE2 on vascular disease outcomes and COVID-19 severity. Additionally, they undertook in silico functional analysis by combining it with other forms of omics data.

They discovered ten loci, eight of them unique, representing 30% of the protein’s inheritance. ACE2 plasma has been shown to be genetically linked to vascular disease, severe COVID-19, and a wide range of complicated disorders and treatments in humans. A Mendelian randomization analysis based on X-chromosome cis-protein quantitative trait loci found that elevated levels of ACE2 were associated with increased severity of COVID-19 (odds ratio, 1.63 [95% CI, 1.10–2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05–2.21]; P=0.03) and infection (odds ratio, 1.60 [95% CI, 1.08–2.37]; P=0.02). Tissue and cell type-specific transcriptome and epigenomic analyzes revealed that regulatory variations in ACE2 were enriched for DNA methylation sites in blood immune cells.

The genetic basis of human plasma ACE2 was shared with cardiovascular disease, COVID-19 and other associated diseases. The genomic architecture of the ACE2 protein has been mapped, providing a resource for future biology and clinical research on this coronavirus receptor.

Reference:www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057888

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