Genetic association of ACE2 rs2285666 (C>T) and rs2106809 (A>G) and susceptibility to SARS-CoV-2 infection among the Ghanaian population

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters human cells using the angiotensin-converting enzyme 2 (ACE-2) receptor. ACE2 single nucleotide polymorphisms (SNPs) can influence susceptibility by affecting viral binding or gene expression. This study investigated the association between ACE2 SNPs, rs2285666 and rs2106809, and the SARS-CoV-2 infection susceptibility in a Ghanaian population.

Methods: Genomic DNA was extracted, using a magnetic bead-based method, from blood samples of a random-subset of 1,334 participants drawn from a two-stage cluster, population-based household cross-sectional SARS-CoV-2 IgG seroprevalence survey. Data collected included, socio-demographic characteristics, medical history, vaccination, and smoking status. Genotyping of the ACE2 SNPs was performed using Allele-Specific Oligonucleotide Polymerase Chain Reaction (ASO-PCR) combined with melting curve analysis. Logistic regression models were utilized to assess the association between the ACE2 SNPs and the susceptibility to SARS-CoV-2 infection.

Results: The median age of participants was 33 [Interquartile range (IQR) = 24-46] years. Females accounted for the majority of the sampled population, 64.3%. SARS-CoV-2-IgG seropositivity was (58.4%, 95%CI: 52.6%-64.2%) among the male population and (54.1%, 95%CI: 49.54%-58.61%) in the female population. There were no significant differences in overall allele or genotype frequencies of ACE2 SNPs between SARS-CoV-2 IgG seropositive and seronegative individuals for both females and males. Among females, those with the T allele of ACE2 rs2285666 had a 38% decreased susceptibility to SARS-CoV-2 infection under the dominant [adjusted odds ratio (aOR) = 0.62; 95%CI = 0.45-0.85, P = 0.003] and heterozygous advantage models (aOR = 0.62; 95%CI = 0.45-0.86, P = 0.004), after adjusting for confounders, but not thee recessive model (aOR = 0.41; 95%CI = 0.03-5.22, P = 0.490). No significant association was observed among males. Overall, the ACE2 rs2106809 was not associated with the susceptibility to SARS-CoV-2 infection in both males and females.

Conclusion: This study found no association between ACE2 rs2106809 genetic variant and susceptibility to SARS-CoV-2 infection, whilst the rs2285666 T-allele was associated with a decreased frequency for SARS-CoV-2 infection among Ghanaian females. These findings enhance our understanding of genetic factors influencing SARS-CoV-2 susceptibility, which could help identify at-risk populations and inform more targeted public health interventions in future outbreaks.

Keywords: SARS-CoV-2 infection (COVID-19); SARS-CoV-2 susceptibility; angiotensin-converting enzyme 2 (ACE2); candidate gene association study (CGAS); genetic epidemiological study; single nucleotide polymorphism (SNP).