Nasal DNA Methylation Architecture of the {ACE2} gene and Epigenetic Aging

Abstract

BACKGROUND AND AIM: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity. The nasal methylome is in direct contact with the environment and might serve as biomarker of COVID-19 disparities by reflecting social and environmental influences on {ACE2} regulation. METHODS: We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm) using the Illumina EPIC array, and tested differences at 15 {ACE2} CpGs by sex, age, race/ethnicity and epigenetic age. We hypothesized that sex, age and race would influence DNA methylation of nasal cells serving as proxy for ACE2 receptors which in turn might be partially influenced by the social and chemical environment. RESULTS:{ACE2} CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean=12.71%) and 3 sites greater DNAm (mean=1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference=3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference=1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference=7.86%) and females (mean absolute difference=8.21%), respectively. CONCLUSIONS:Nasal {ACE2} DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences. Findings need to be confirmed among adults and patients with risk factors for COVID-19 severity. KEYWORDS: Epigenetics, Disparities, COVID-19