Table 1. Genetic and epigenetic variations in ACE2 and their way to modulate ACE2 protein and/or different virus entry.
ACE2 gene | Variation, MAF (%) | Effect on protein, virus interaction or infection | Ref. |
---|---|---|---|
Genetic variations in exons | rs73635825A >G (S19P), G:0–0.1 | Affecting intermolecular interaction with the coronavirus spike protein | [18] |
Interaction-booster between ACE2 and S1 | [19] | ||
rs143936283T >C (E329G), C: <0.02 | Affecting intermolecular interaction with the coronavirus spike protein | [18] | |
rs778030746T >C (I21V), C:<0.002; rs1244687367A >G (I21T), G: <0.001; rs756231991C >T (E23K), T:<0.001; rs1434130600C >T (A25T), T: <0.001; rs4646116T >C (K26R), C: 2–9; | Interaction-booster between ACE2 and S1 | [19] | |
rs781255386T >C (T27A), C: 0.001; rs778500138T >A (E35D), A: 0–0.3; rs1199100713A >T (N64K), T: <0.001; rs867318181T >C (E75G), C: <0.001; rs763395248G >A (T92I), A: <0.002; rs1395878099T >G (Q102P), G: <0.004; rs142984500T >C (H378R), C: 0.007–0.02; rs1348114695C >T (E35K), T:<0.002; rs146676783C >T (E37K); T: 0.002–0.003; rs1192192618T >A (Y50F), A: <0.001; rs760159085T >C (N51D), C: <0.001; rs1569243690T >C (N51S), C: <0.001; rs1325542104T >C (M62V), C: <0.02; rs755691167T >C (K68E), C: <0.001; rs1256007252A >C (F72V), C: <0.001; rs766996587C >A, T (M82I), T: 0.001–0.01; rs759579097C >T (G326E), T: <0.001; rs143936283T >C (E329G), C: 0.01–0.03; rs370610075C >A (G352V), A: 0.001–0.01; rs961360700C >T (D355N), T: <0.01; rs751572714T >A (Q388L), 0.002–0.004; rs762890235G >T (P389H), T: 0.002–0.004; rs1016409802T >C (H505R), Unknown; rs1352194082G >A, C (R514G/*), C: <0.001; rs1263424292T >C (Y515C), C: <0.001 | Interaction-inhibitor between ACE2 and S1 | [19] | |
Genetic variations in introns | rs2106809A >G (intron 1), G: 18–32 | No effect on circulating ACE2 levels | [16] |
No association with SARS poor outcomes | [20] | ||
rs4646155C >T (intron 8), T: 0–6 | No effect on circulating ACE2 levels | [16] | |
rs879922G >C (intron 11), C: 32–39 | No effect on circulating ACE2 levels | [16] | |
Lower ACE2 expression in CC | [14] | ||
rs2285666G >A (intron 3), A:18 | Decreased ACE2 expression in AA | [17] | |
No association with SARS poor outcomes | [20] | ||
No association with SARS process | [21] | ||
rs4646142G >A, C (intron 7), C: 20–48; rs714205C >G (intron 16), G: 17–49; rs2074192C >T (intron 16), T: 36–47 | No association with SARS poor outcomes | [20] | |
Epigenetic changes: DNA methylation | ChrX: 15621573–15622147 | Gender differences in the methylation of specific CpG sites in healthy individuals | [22] |
Epigenetic changes: microRNAs | miR-421, miR-143 | Are among known ACE2 expression regulators | [23] |
miR-200b, hsa-miR-200c and hsa-miR-429 | Predicted miR binding site | [24] | |
miR-200c-3p | Mi-R upregulated by avian influenza virus H5N1 | [25] | |
Epigenetic changes: histone modifications | HAT1, HDAC2 and KDM5B | ACE2 regulation in the lung | [26] |
JAK–STAT pathway | ACE2 gene regulation | [27] |
MAF: Minor Allele Frequency; SARS: Severe Acute Respiratory Syndrome.