SARS-CoV-2感染的症状差异很大,从无症状病例到以急性呼吸窘迫综合征为特征的严重形式,多器官损伤,和死亡。研究表明,特定基因与SARS-CoV-2感染易感性和疾病严重程度之间存在相关性,特别涉及与炎症和免疫反应相关的基因变异。本研究的目的是研究白细胞介素-6(IL-6)启动子区域的rs1800795(-174G>C)和rs1800797(-597A>G)变体与SARS-CoV-2感染易感性之间的关系。此外,我们旨在探讨摩洛哥人群中它们与COVID-19严重程度的相关性。在这项病例对照研究中,我们招募了270名未接种疫苗的COVID-19患者,由132例重度COVID-19和138例无症状中度COVID-19组成。此外,纳入339例SARS-CoV-2阴性组。使用预先设计的TaqManSNP基因分型进行IL-6基因的rs1800795和rs1800797多态性的基因分型。SARS-CoV-2阴性对照的中位年龄为50岁,而重症COVID-19病例的中位年龄为61岁。此外,无症状至中度COVID-19患者的中位年龄为36岁.我们观察到重度和轻度COVID-19患者之间的年龄差异显着(p<0.0001),性别与COVID-19严重程度之间存在关联(p=0.011)。IL-6-597G>A和-174G>C变体的等位基因和基因型频率与SARS-CoV-2感染的易感性没有显着关联(p>0.05)。然而,进一步分析显示,rs1800797和rs1800795之间的连锁不平衡表明GC*单倍型(OR=0.04,95%CI0.01-0.30,p=0.001)和AG*单倍型(OR=0.11,95%CI0.03-0.46,p=0.002)个体与SARS-CoV-2感染的保护作用显著相关.此外,在占主导地位的模型中,与G/G-C/C基因型相比,IL-6-174G/C基因型对严重疾病的发展具有保护作用(p=0.03;OR=0.41,95%CI0.18-0.96).然而,全血细胞计数标记之间的相关性,血液学标志物,D-二聚体,C反应蛋白,根据-597A>G和-174G>C基因型,铁蛋白水平没有显着差异(均p>0.05)。我们的发现为COVID-19的发病机理提供了有价值的见解,表明IL-6基因的遗传变异可能导致摩洛哥人群对严重SARS-CoV-2感染的易感性。
The symptoms of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to severe forms marked by acute respiratory distress syndrome, multi-organ damage, and fatalities. Studies indicate a correlation between specific genes and susceptibility to SARS-CoV-2 infection and disease severity, particularly involving variants in genes linked to inflammation and immune responses. The objective of this study is to investigate the association between rs1800795 (- 174 G > C) and rs1800797 (- 597 A > G) variants in the interleukin-6 (IL-6) promoter region and susceptibility to SARS-CoV-2 infection. Additionally, we aim to explore their correlation with COVID-19 severity in a Moroccan population. In this case-control study, we enrolled 270 unvaccinated COVID-19 patients, consisting of 132 with severe COVID-19 and 138 with asymptomatic-moderate COVID-19. Additionally, we included 339 SARS-CoV-2-negative group. Genotyping of rs1800795 and rs1800797 polymorphisms of the IL-6 gene was performed using predesigned TaqMan SNP genotyping. The median age of SARS-CoV-2-negative controls was 50 years, while severe COVID-19 cases exhibited a median age of 61 years. Additionally, individuals with asymptomatic to moderate COVID-19 had a median age of 36 years. We observed a significant age difference between severe and mild COVID-19 patients (p < 0.0001), and an association was noted between gender and the severity of COVID-19 (p = 0.011). The allele and genotype frequencies of the IL-6 - 597G > A and - 174G > C variants did not show significant associations with susceptibility to SARS-CoV-2 infection (p > 0.05). However, further analysis revealed that the linkage disequilibrium between rs1800797 and rs1800795 indicated that individuals with the GC* haplotype (OR = 0.04, 95% CI 0.01-0.30, p = 0.001) and AG* haplotype (OR = 0.11, 95% CI 0.03-0.46, p = 0.002) were significantly associated with protection against SARS-CoV-2 infection. Moreover, in the overdominant model, the IL-6 - 174 G/C genotype was found to be protective against the development of severe disease compared to those with the G/G-C/C genotypes (p = 0.03; OR = 0.41, 95% CI 0.18-0.96). However, correlations between complete blood count markers, hematological markers, D-dimer, C-reactive protein, and ferritin levels according to - 597 A > G and - 174G > C genotypes showed no significant differences (all p > 0.05). Our findings provide valuable insights into the pathogenesis of COVID-19, suggesting that genetic variations at the IL-6 gene may contribute to the susceptibility to severe SARS-CoV-2 infection within the Moroccan population.