PDF(Pubmed)
Abstract：
COVID-19 has a broad clinical spectrum, ranging from asymptomatic-mild form to severe phenotype. The severity of COVID-19 is a complex trait influenced by various genetic and environmental factors. Ethnic differences have been observed in relation to COVID-19 severity during the pandemic. It is currently unknown whether genetic variations may contribute to the increased risk of severity observed in Latin-American individuals The aim of this study is to investigate the potential correlation between gene variants at CCL2, OAS1, and DPP9 genes and the severity of COVID-19 in a population from Quito, Ecuador. This observational case-control study was conducted at the Carrera de Biologia from the Universidad Central del Ecuador and the Hospital Quito Sur of the Instituto Ecuatoriano de Seguridad Social (Quito-SUR-IESS), Quito, Ecuador. Genotyping for gene variants at rs1024611 (A>G), rs10774671 (A>G), and rs10406145 (G>C) of CCL2, OAS1, and DPP9 genes was performed on 100 COVID-19 patients (43 with severe form and 57 asymptomatic-mild) using RFLP-PCR. The genotype distribution of all SNVs throughout the entire sample of 100 individuals showed Hardy Weinberg equilibrium (P=0.53, 0.35, and 0.4 for CCL2, OAS1, and DPP9, respectively). The HWE test did not find any statistically significant difference in genotype distribution between the study and control groups for any of the three SNVs. The multivariable logistic regression analysis showed that individuals with the GG of the CCL2 rs1024611 gene variant had an increased association with the severe COVID-19 phenotype in a recessive model (P = 0.0003, OR = 6.43, 95% CI 2.19-18.89) and for the OAS1 rs10774671 gene variant, the log-additive model showed a significant association with the severe phenotype of COVID-19 (P=0.0084, OR=3.85, 95% CI 1.33-11.12). Analysis of haplotype frequencies revealed that the coexistence of GAG at CCL2, OAS1, and DPP9 variants, respectively, in the same individual increased the presence of the severe COVID-19 phenotype (OR=2.273, 95% CI: 1.271-4.068, P=0.005305). The findings of the current study suggests that the ethnic background affects the allele and genotype frequencies of genes associated with the severity of COVID-19. The experience with COVID-19 has provided an opportunity to identify an ethnicity-based approach to recognize genetically high-risk individuals in different populations for emerging diseases.
摘要：
COVID-19具有广泛的临床谱，从无症状-轻度形式到严重表型。COVID-19的严重程度是受多种遗传和环境因素影响的复杂性状。在大流行期间，观察到与COVID-19严重程度有关的种族差异。目前尚不清楚遗传变异是否会导致在拉丁美洲个体中观察到的严重程度风险增加。这项研究的目的是调查CCL2，OAS1和DPP9基因的基因变异与COVID-19在基多人群中的严重程度之间的潜在相关性，厄瓜多尔。这项观察性病例对照研究是在厄瓜多尔中央大学的CarreradeBiologia和厄瓜多尔社会研究所（Quito-SUR-IESS）的QuitoSur医院进行的，基多,厄瓜多尔。rs1024611基因变异的基因分型(A>G)，rs10774671(A>G),使用RFLP-PCR对100例COVID-19患者（43例严重形式，57例无症状轻度）进行CCL2，OAS1和DPP9基因的rs10406145（G>C）。在整个100个个体的整个样本中，所有SNV的基因型分布均显示出HardyWeinberg平衡（CCL2，OAS1和DPP9的P分别为0.53、0.35和0.4）。对于三种SNV中的任何一种,HWE检验在研究组和对照组之间的基因型分布没有发现任何统计学上的显著差异。多变量逻辑回归分析显示，在隐性模型中，具有CCL2rs1024611基因变异的GG的个体与严重COVID-19表型的相关性增加（P=0.0003，OR=6.43，95％CI2.19-18.89），对于OAS1rs10774671基因变异，对数累加模型显示与COVID-19的严重表型显著相关(P=0.0084,OR=3.85,95%CI1.33~11.12).对单倍型频率的分析表明，GAG在CCL2，OAS1和DPP9变体中共存，分别,在同一个体中，严重COVID-19表型的存在增加(OR=2.273，95%CI：1.271-4.068，P=0.005305)。当前研究的结果表明，种族背景会影响与COVID-19严重程度相关的基因的等位基因和基因型频率。COVID-19的经验为确定一种基于种族的方法提供了机会，以识别不同人群中新兴疾病的遗传高风险个体。
