Supplementary file 1_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。血管紧张素转换酶2的单核苷酸多态性（single nucleotide polymorphisms, SNPs）可通过影响病毒结合或基因表达，改变宿主对SARS-CoV-2的感染易感性。本研究针对加纳人群，探究了ACE2基因的rs2285666与rs2106809两个单核苷酸多态性位点与SARS-CoV-2感染易感性之间的关联。
方法：本研究从一项两阶段整群抽样的人群家庭横断面SARS-CoV-2 IgG血清流行病学调查中，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。收集的研究数据包括社会人口学特征、病史、疫苗接种情况以及吸烟状态。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基因的单核苷酸多态性进行基因分型。采用logistic回归模型，评估ACE2基因单核苷酸多态性与SARS-CoV-2感染易感性之间的关联。
结果：参与者的年龄中位数为33岁[四分位间距（interquartile range, IQR）=24~46岁]。女性占总抽样人群的64.3%，为主要受试群体。男性人群中SARS-CoV-2 IgG血清阳性率为58.4%（95%置信区间：52.6%~64.2%），女性人群中则为54.1%（95%置信区间：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基因单核苷酸多态性的总体等位基因频率或基因型频率均无显著差异。在校正混杂因素后，显性遗传模型[校正比值比（adjusted odds ratio, aOR）=0.62；95%置信区间：0.45~0.85，P=0.003]和杂合子优势模型（aOR=0.62；95%置信区间：0.45~0.86，P=0.004）下，携带ACE2 rs2285666位点T等位基因的女性感染SARS-CoV-2的易感性降低38%；但隐性遗传模型中未观察到该关联（aOR=0.41；95%置信区间：0.03~5.22，P=0.490）。男性人群中未观察到此类关联。总体而言，无论男性还是女性，ACE2 rs2106809位点均与SARS-CoV-2感染易感性无显著关联。
结论：本研究发现，ACE2 rs2106809基因变异与SARS-CoV-2感染易感性无显著关联；而在加纳女性人群中，rs2285666位点的T等位基因与SARS-CoV-2感染率降低相关。本研究结果加深了我们对影响SARS-CoV-2感染易感性的遗传因素的理解，有助于识别感染高风险人群，为未来疫情中的针对性公共卫生干预措施提供参考依据。