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Table. 1.

Table. 1.

ACE2 variants and expression cause inter-individual variability and susceptibility to COVID-19 in different populations

Population Reference Method Variants Interpretation Effect on ACE2
Italian population [6] Computational study using Network of Italian Genomes database rs775181355 207 G>Tor p.Val506Ala p.Val506Ala is indeed the only AA change reported in the European non-Finnish population Predicted as probably damaging for ACE2 protein structure by PolyPhen and deleterious by SIFT
Italian population [6] Computational study using Networkof Italian Genomes database p.Asn720Asp, p.Lys26Arg, and p.Gly211Arg These variants are moderately expressed in Italian and European populations; they do not occur in the Eastern Asia population Predicted to interfere with SARS-CoV-2 spike protein, thus destabilizing the protein structure
[27] Homology modelling predicted ACE2 allelic variants rs73635825 (S19P) and rs143936283 (E329G) Intrinsic resistance with these alleles owing to low binding affinity Normal ACE2 expression but lack of some key residues in complex formation with SARS-CoV-2 spike protein
Population allele frequencies from 1,000 Genomes Phase 3 [31] eQTLs in many tissues, from GTEx database 38 most significant eQTLs in ACE2 High (close to 100%) allele frequency in East Asians All are positively correlated with higher ACE2 expression, indicative of their contributions to higher ACE2 expression in East Asians
East Asian, European, African, South Asian, mixed American [32] eQTL variants using GTEx database rs4646127, rs2158082, rs5936011, rs6629110, rs4830983, and rs5936029 Major allele frequency (most common variant) is high (>95%) in East Asian population Higher major allele frequency is associated with greater susceptibility and higher ACE2 expression.
Lys26Arg, Ile486Val, Ala627Val, Asn638Ser, Ser692Pro, Asn720Asp, and Leu731Ile/P compared with the European population (<50-60%)
European and East Asian [45] eQTLs variants, from GTEx database rs2285666 (also called G8790A) The A allele is more frequent in the Italian population The AA genotype confers higher ACE2 expression level
European and East Asian populations [45] eQTLs variants, from GTEx database rs463727, rs34624090, rs55964536, rs734056, rs4290734, rs34783969, rs11702475, rs35899679, and rs35041537 SNVs frequent in European population, whereas totally absent in Asian population Two haplotypes were supposed to increase TMPRSS2 expression in an androgen-specific way

Abbreviations: ACE2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019; SNV, single nucleotide variant; eQTL, expression quantitative trait loci; GTEx, genotype-tissue expression; PolyPhen, Variant phenotyping; SIFT, sorting intolerant from tolerant; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; AA, amino acid.

Ann Lab Med 2021;41:129~138 https://doi.org/10.3343/alm.2021.41.2.129

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