Abstract
Background: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. “cytokine storm”). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites.
Methods: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent neoplasia or inflammation were used for this study. Total mRNA was isolated and subjected to real-time polymerase chain reaction for ACE2, and TMPRSS2 was assessed from non-Hispanic Blacks (n = 45) and non-Hispanic Whites (n = 38). GAPDH and beta-actin were used for normalization. Multivariable analysis was performed using Analyse-IT software.
Results: ACE2 and TMPRSS2 levels were not altered by gender, BMI, or age. ACE2 levels were lower in Blacks than Whites achieving statistical significance in multivariable (0.51-fold, p = 0.03) but not quite in univariable (p = 0.07) analysis. This downregulation was mirrored in TMRPSS2 in both univariable (p = 0.03) and multivariable analyses (0.41-fold, p = 0.02). Moreover, there was a strong correlation between ACE2 and TMPRSS2 levels (r-squared = 0.78).
Conclusions: To our knowledge, this is the first report on racial differences inACE2 and TMPRSS2 mucosal expression. This may provide potential biological underpinnings for the disproportionately higher mortality of Covid-19 in Blacks and should spur future studies.
Keywords: ACE2; Covid-19; Racial disparities; TMPRSS2.
【저자키워드】 COVID-19, ACE2, TMPRSS2., Racial disparities, 【초록키워드】 Inflammation, TMPRSS2, Cytokine storm, immune response, Mortality, knowledge, susceptibility, severity, Infection, Gender, protease, angiotensin-converting enzyme 2, polymerase chain reaction, mRNA, real-time polymerase chain reaction, Beta, age, targets, BMI, correlation, transmembrane protease serine 2, expression, epithelial, mechanism, Angiotensin-converting enzyme, mucosal, Inflammatory response, Analysis, angiotensin, biopsy, epithelial cell, Chain Reaction, not altered, black, Racial, Serine, Perspective, COVID-19 infections, statistical significance, multivariable analysis, host protein, white, concert, transmembrane, fold, downregulation, normalization, multivariable analyses, neoplasia, GAPDH, Actin, rectal mucosa, TMPRSS2 levels, serine 2, cell receptor, TMRPSS2, TMPRSS2 level, polymerase chain, beta-actin, multivariable, was performed, were used, suppress, Total, multivariable analysis, univariable, 【제목키워드】 disparity, black, Potential,