Colonic Epithelial Angiotensin-Converting Enzyme 2 (ACE2) Expression in Blacks and Whites: Potential Implications for Pathogenesis Covid-19 Racial Disparities.

Abstract

BackgroundCovid-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.MethodsArchived 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.ResultsACE2 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).ConclusionsTo 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.