Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (–597G > A and –174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (–174G > C) and rs1800797 (–597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (–174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (–597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having ‘C’ allele of IL6 (–174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (–174G > C) and rs1800797 (–597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that ‘C’ allele of rs1800795 (–174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.

中文翻译：

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IL6 基因 –174G > C 和 –597G > A 的遗传多态性与 COVID-19 严重程度的风险相关

2019 冠状病毒病 (COVID-19) 是一种以急性呼吸窘迫综合征为特征的促炎性疾病。白细胞介素 6 是巨噬细胞分泌的一种细胞因子，可介导炎症反应，其水平经常升高，并且与 COVID-19 患者的严重程度相关。COVID-19患者中IL6细胞因子的差异表达可能与细胞因子基因调控区中单核苷酸多态性（SNP）的存在有关。本研究的目的是调查IL6基因的两个启动子多态性（–597G > A 和 –174G > C）与 COVID-19 严重程度的作用。该研究纳入了 242 名患者，其中 97 名有严重症状的 COVID-19 患者，145 名有轻微症状的 COVID-19 患者。通过聚合酶链反应-限制性片段长度多态性 (PCR-RFLP) 对IL6基因启动子区域的两个选定的 SNP（rs1800795 (–174G > C) 和 rs1800797 (–597G > A)）进行基因分型。在我们的研究中，具有IL6 (–174G > C) 多态性GC 基因型的个体表现出明显较高的严重风险 [调整后的赔率 (OR) 3.86，p  <.001]，但我们没有观察到 COVID-19 严重程度与 rs1800797 之间存在任何关联(–597G > A) 多态性。具有IL6 'C' 等位基因(–174G > C) 多态性的个体的 COVID-19 严重程度显着更高 ( p  = .014)。rs1800795 (–174G > C) 和 rs1800797 (–597G > A) 之间的连锁不平衡表明，具有 AC* 单倍型的个体与 COVID-19 严重程度显着相关 ( p  = .034)。我们的结果表明， IL6 rs1800795 (–174G > C) 多态性的“C”等位基因可能是北印度人群中 COVID-19 严重程度的风险等位基因。