Table 3_Genetic association of ACE2 rs2285666 (C>T) and rs2106809 (A>G) and susceptibility to SARS-CoV-2 infection among the Ghanaian population.docx

BackgroundSevere 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.
MethodsGenomic 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
ResultsThe 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.
ConclusionThis 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.

背景：严重急性呼吸综合征冠状病毒2（Severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）通过血管紧张素转换酶2（angiotensin-converting enzyme 2，ACE-2）受体侵入人体细胞。ACE2单核苷酸多态性（single nucleotide polymorphisms，SNPs）可通过影响病毒结合或基因表达，进而影响个体对病毒的感染易感性。本研究旨在探究加纳人群中ACE2单核苷酸多态性rs2285666与rs2106809与SARS-CoV-2感染易感性之间的关联。
方法：研究对象来自两阶段整群抽样的基于人群的家庭横断面SARS-CoV-2 IgG血清流行率调查，随机抽取1334名参与者的血液样本，采用磁珠法提取基因组DNA。收集的资料包括社会人口学特征、病史、疫苗接种情况及吸烟状态。采用等位基因特异性寡核苷酸聚合酶链反应（Allele-Specific Oligonucleotide Polymerase Chain Reaction，ASO-PCR）结合熔解曲线分析法对ACE2单核苷酸多态性进行基因分型。采用logistic回归模型评估ACE2单核苷酸多态性与SARS-CoV-2感染易感性之间的关联。
结果：参与者的中位年龄为33岁[四分位间距（Interquartile range，IQR）=24~46岁]。女性占抽样人群的多数，为64.3%。男性人群中SARS-CoV-2 IgG血清阳性率为58.4%（95%置信区间（confidence interval，CI）：52.6%~64.2%），女性人群中为54.1%（95%CI：49.54%~58.61%）。无论男性还是女性，SARS-CoV-2 IgG血清阳性与血清阴性个体之间，ACE2单核苷酸多态性的总体等位基因或基因型频率均无显著差异。在女性群体中，携带ACE2 rs2285666 T等位基因的个体在显性模型[校正比值比（adjusted odds ratio，aOR）=0.62；95%CI=0.45~0.85，P=0.003]和杂合子优势模型（aOR=0.62；95%CI=0.45~0.86，P=0.004）下，经混杂因素校正后，SARS-CoV-2感染易感性降低38%，但在隐性模型中未观察到该关联（aOR=0.41；95%CI=0.03~5.22，P=0.490）。男性群体未观察到显著关联。总体而言，ACE2 rs2106809与男性和女性群体的SARS-CoV-2感染易感性均无显著关联。
结论：本研究发现ACE2 rs2106809基因变异与SARS-CoV-2感染易感性无关联，而rs2285666 T等位基因与加纳女性群体中SARS-CoV-2感染频率降低相关。这些发现加深了我们对影响SARS-CoV-2易感性的遗传因素的理解，有助于识别感染高危人群，并为未来疫情中制定更具针对性的公共卫生干预措施提供依据。