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. 2021 Mar 29;11(1):7107.
doi: 10.1038/s41598-021-86494-7.

DNA methylation architecture of the ACE2 gene in nasal cells of children

Andres Cardenas  1   2 , Sheryl L Rifas-Shiman  3 , Joanne E Sordillo  3 , Dawn L DeMeo  4 , Andrea A Baccarelli  5 , Marie-France Hivert  3   6 , Diane R Gold #  4   7 , Emily Oken #  3
Affiliations

DNA methylation architecture of the ACE2 gene in nasal cells of children

Andres Cardenas et al. Sci Rep. .

Abstract

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.1,2 The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. 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. 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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
(A) Boxplots of DNA methylation in nasal cells for the angiotensin-converting enzyme 2 (ACE2) gene by sex among 15 CpG sites. (B) Spearman correlation coefficients of nasal cell DNA methylation levels among CpGs found in the angiotensin-converting enzyme (ACE2) gene. (C) Local Manhattan plot for the association of ACE2 DNA methylation for Hispanic relative to white females. Spearman correlation matrix for CpGs among all females. (D) Local Manhattan plot for the association of ACE2 DNA methylation for Black relative to white males. Spearman correlation matrix for CpGs among all males.
Figure 1
Figure 1
(A) Boxplots of DNA methylation in nasal cells for the angiotensin-converting enzyme 2 (ACE2) gene by sex among 15 CpG sites. (B) Spearman correlation coefficients of nasal cell DNA methylation levels among CpGs found in the angiotensin-converting enzyme (ACE2) gene. (C) Local Manhattan plot for the association of ACE2 DNA methylation for Hispanic relative to white females. Spearman correlation matrix for CpGs among all females. (D) Local Manhattan plot for the association of ACE2 DNA methylation for Black relative to white males. Spearman correlation matrix for CpGs among all males.
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