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ACE and ARB blood pressure meds (i.e losartan) and coronavirus concern
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<blockquote data-quote="tareload" data-source="post: 174761"><p><a href="http://Individual%20variation%20of%20the%20SARS-CoV2%20receptor..." target="_blank">https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=2ahUKEwj4soumx7noAhUllXIEHck4A-cQFjAAegQIAxAB&url=https%3A%2F%2Fwww.preprints.org%2Fmanuscript%2F202003.0191%2Fv1%2Fdownload&usg=AOvVaw3UdwZHpkfhHkpFokMMgflX</a></p><p></p><p>Recent preprint:</p><p></p><p>Discussion</p><p>In summary, through integrating public genomics, epigenomics and transcriptomics</p><p>data, we examined whether variation of the SARS-CoV2 receptor ACE2 gene</p><p>expression in different tissues across individuals can explain the differences in</p><p>infection susceptibility and outcome. <em>Our findings are contrary to the expectation from</em></p><p><em>ACE2 being only a receptor for the virus, instead, its expression level is high in Asian</em></p><p><em>females and young people (Fig. 1 and Table 1), those who are known to be less</em></p><p><em>susceptible, and even less inflicted by severe or fatal outcome, while it is low in males,</em></p><p><em>further decrease with age and T2D, those who are most susceptible to bad outcome</em></p><p><em>(Fig. 1 and 3), suggesting at a population level a negative correlation between ACE2</em></p><p><em>expression and CovID19 severity and fatality.</em></p><p>At the molecular level, we found ACE2 anti-expressed genes in most tissues</p><p>and cells are highly enriched for virus infection pathways (Fig. 3a), estrogen strongly</p><p>and androgen moderately increase ACE2 expression in mouse and human tissues</p><p>(Fig. 2), whereas severe CoVID-19 induced IL-2 and IL7 repress ACE2 expression in</p><p>mouse T cells, and T2D reduced ACE2 expression and ACE2 expressing cells in</p><p>human tissues (Fig. 3). The effect of estrogen, androgen and cytokines are reflected</p><p>on clusters of estrogen and androgen receptors, STAT5, JUN, MYC and other TFs</p><p>binding at ACE2 regulatory regions, where hypertension QTLs and the great majority</p><p>of ACE2 eQTLs are also mapped to. Finally, as the eQTLs that show largest allele</p><p>frequency differences between ethnic groups are also the ones having close to full</p><p>penetrance in East Asians and also the strongest positive eQTLs on ACE2 expression</p><p>(Table 1), ACE2 expression differences among ethnic groups are indeed genetically</p><p>coded, which may also contribute to the differences in SARS-CoV2 infection outcome.</p><p>Our results established a counter argument against the speculation that high</p><p>ACE2 is a culprit in CoVID-19 outcome, and on the contrary supports a protective role</p><p>of high ACE2 expression against SARS-CoV2 fatality (Fig. 3h). The exceptionally</p><p>elevated basal level of ACE2 in Asian females (Fig. 1) and the strong positive ACE2</p><p>eQTLs in East Asians (Table 1) suggest that it could be the Asian females are more</p><p>protected against SARS-CoV and SARS-CoV2 severe symptoms rather than males</p><p>being more susceptible. Although we have analyzed thousands of samples, the sizes</p><p>of Asian samples and samples for some tissues are still small compared to others, it</p><p>remains to be seen whether larger samples will reveal similar patterns in the future</p><p>when more data become available.</p><p></p><p><em>The repression of ACE2 might be counteracted by higher basal ACE2 level,</em></p><p><em>which is inducible by higher sex hormone levels (that decrease with age) and</em></p><p><em>repressed by systemic inflammation (that increase with age and chronic diseases) (Fig.</em></p><p><em>2 and 3). For SARS-CoV2, the decrease of ACE2 might be further exacerbated by the</em></p><p><em>direct binding and consumption of ACE2 protein by the virus. Before the availability of</em></p><p><em>an effective vaccine to prevent SARS-CoV2 infection, a major task is to understand</em></p><p><em>the variations in severity and fatality of the infection in human populations, to which</em></p><p><em>ACE2 might be one of the contributors. Fortunately, the low ACE2 activity can be</em></p><p><em>rescued by dampening its negatively regulated downstream targets such as</em></p><p><em>angiotensin II or its receptors, such as by angiotensin II antagonist losartan 27.</em></p></blockquote><p></p>
[QUOTE="tareload, post: 174761"] [URL='http://Individual%20variation%20of%20the%20SARS-CoV2%20receptor...']https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=2ahUKEwj4soumx7noAhUllXIEHck4A-cQFjAAegQIAxAB&url=https%3A%2F%2Fwww.preprints.org%2Fmanuscript%2F202003.0191%2Fv1%2Fdownload&usg=AOvVaw3UdwZHpkfhHkpFokMMgflX[/URL] Recent preprint: Discussion In summary, through integrating public genomics, epigenomics and transcriptomics data, we examined whether variation of the SARS-CoV2 receptor ACE2 gene expression in different tissues across individuals can explain the differences in infection susceptibility and outcome. [I]Our findings are contrary to the expectation from ACE2 being only a receptor for the virus, instead, its expression level is high in Asian females and young people (Fig. 1 and Table 1), those who are known to be less susceptible, and even less inflicted by severe or fatal outcome, while it is low in males, further decrease with age and T2D, those who are most susceptible to bad outcome (Fig. 1 and 3), suggesting at a population level a negative correlation between ACE2 expression and CovID19 severity and fatality.[/I] At the molecular level, we found ACE2 anti-expressed genes in most tissues and cells are highly enriched for virus infection pathways (Fig. 3a), estrogen strongly and androgen moderately increase ACE2 expression in mouse and human tissues (Fig. 2), whereas severe CoVID-19 induced IL-2 and IL7 repress ACE2 expression in mouse T cells, and T2D reduced ACE2 expression and ACE2 expressing cells in human tissues (Fig. 3). The effect of estrogen, androgen and cytokines are reflected on clusters of estrogen and androgen receptors, STAT5, JUN, MYC and other TFs binding at ACE2 regulatory regions, where hypertension QTLs and the great majority of ACE2 eQTLs are also mapped to. Finally, as the eQTLs that show largest allele frequency differences between ethnic groups are also the ones having close to full penetrance in East Asians and also the strongest positive eQTLs on ACE2 expression (Table 1), ACE2 expression differences among ethnic groups are indeed genetically coded, which may also contribute to the differences in SARS-CoV2 infection outcome. Our results established a counter argument against the speculation that high ACE2 is a culprit in CoVID-19 outcome, and on the contrary supports a protective role of high ACE2 expression against SARS-CoV2 fatality (Fig. 3h). The exceptionally elevated basal level of ACE2 in Asian females (Fig. 1) and the strong positive ACE2 eQTLs in East Asians (Table 1) suggest that it could be the Asian females are more protected against SARS-CoV and SARS-CoV2 severe symptoms rather than males being more susceptible. Although we have analyzed thousands of samples, the sizes of Asian samples and samples for some tissues are still small compared to others, it remains to be seen whether larger samples will reveal similar patterns in the future when more data become available. [I]The repression of ACE2 might be counteracted by higher basal ACE2 level, which is inducible by higher sex hormone levels (that decrease with age) and repressed by systemic inflammation (that increase with age and chronic diseases) (Fig. 2 and 3). For SARS-CoV2, the decrease of ACE2 might be further exacerbated by the direct binding and consumption of ACE2 protein by the virus. Before the availability of an effective vaccine to prevent SARS-CoV2 infection, a major task is to understand the variations in severity and fatality of the infection in human populations, to which ACE2 might be one of the contributors. Fortunately, the low ACE2 activity can be rescued by dampening its negatively regulated downstream targets such as angiotensin II or its receptors, such as by angiotensin II antagonist losartan 27.[/I] [/QUOTE]
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ACE and ARB blood pressure meds (i.e losartan) and coronavirus concern
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